Spinal Muscular Atrophy (SMA)

Introduction[edit | edit source]

Spinal Muscular Atrophy (SMA) is a genetic disorder also considered to be a neurodegenerative disorder, specifically a motor neurone disease. SMA is characterised by the degeneration of alpha motor neurons in the spinal cord, affecting the control of voluntary muscle movement.[1] It occurs in roughly one in 6,000–10,000 births.[2] There are several classifications of SMA, which are assigned based on the age at which symptoms first occur along with the highest level of muscle activation attained or expected to be attained. [1][3]

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Pathological Process[edit | edit source]

SMA is considered to be an autosomal recessive condition resulting from the homozygous deletion of the gene SMN1 (survival of motor neuron 1).[2] In some cases, it is possible for the neighboring SMN2 gene to compensate for a lack of the SMN1 gene. Therefore, if there is one or more additional copies of the SMN2 gene, later-onset and less severe SMA symptoms can occur.[3]

Autosomal Recessive

Clinical Presentation and Classification[edit | edit source]

SMA is classified based on the age at which symptoms first occur as well as the level of muscle activation attained or expected to be attained. [1][3]SMA symptoms range in severity but often include hypotonia, muscle weakness (proximal muscles greater than distal muscles and lower extremity than upper extremity), bone or joint issues, difficulty swallowing, and/or difficulty breathing.[3][5]

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Types of SMA[edit | edit source]

TYPE 1 (MOST SEVERE)(Werdnig-Hoffmann disease of acute infantile SMA) TYPE 2 TYPE 3 (Kugelberg-Welander syndrome or juvenile SMA) TYPE 4
AGE OF ONSET First 6 months 6-18 months 18 months or older Adulthood (after 21 years)
SYMPTOMS
  • Reduce muscle tone
  • Contractures
  • Reflexes absent
  • Swallowing,feeding difficulty
  • Can sit
  • Unable to stand/walk without support
  • Respiratory difficulties
  • Walk independently
  • Difficulty in running, stair climbing
  • Scoliosis
Mild to moderate leg weakness.
LIFE EXPENTANCY Die before 2 years [3] Adolescence or young adulthood [3] Normal lifespan (with regular physical rehabilitations) [3] Normal lifespan(with little physical training) [3]

Diagnostic Procedures[edit | edit source]

Diagnosis generally starts with genetic testing to determine whether or not the SMN1 gene is absent. Genetic testing has been found to have a 95% sensitivity (test shows the absence of SMN1 the gene when it is truly absent) and an almost 100% specificity (test shows the presence of SMN the gene when it is truly present). If genetic testing does return a result consistent with clinical signs and symptoms, additional testing in the form of electrocardiography, a muscle biopsy, a nerve conduction velocity study, or blood tests can be performed.[3][7]

Differential Diagnosis[edit | edit source]

DD of spinal Muscular Atrophy[8]

Outcome Measures[edit | edit source]

There are several outcome measures which can be used to detect changes in the course of treatment for patients with SMA. These tools should be appropriately selected according to the age and severity of the disease.

  • Six-Minute Walking Test (6MWT) - The Six-Minute-Walking-Test can be safely performed in ambulant patients with SMA. It has been proven to detect fatigue-related changes in this population of patients and also correlates with other established outcome measures for patients with spinal muscular atrophy[9].
  • Revised Hammersmith Scale for SMA (RHS) - The RHS is predominantly used in patients with SMA types 2 and 3. In combination with the World Health Organisation (WHO) motor milestones, the scale can be more sensitive toward the description of the SMA phenotype. The RHS has been designed to capture a wide range of abilities across a broad spectrum of SMA, from very young children to adolescents and adults[2].
  • WHO Developmental Milestones - The WHO scales aim to link the growth of the child and motor development in one single reference. The final version of the protocol includes six items: "Sitting without support," "hands-and-knees crawling," "standing with assistance," "walking with assistance," "standing alone," and "walking alone.". The WHO provides important information about a child's gross motor development in different cultural settings[10].
  • Revised Upper Limb Module (RULM) for SMA - The RULM is a specifically designed outcome measure for upper limb function in patients with Spinal muscular atrophy. The scale has shown good reliability and validity, which makes it a good choice for assessing arm function in children and adults with SMA[11].

Management / Interventions[edit | edit source]

The management of SMA warrants a multi-disciplinary approach coordinated by the patient's primary clinician.[12]

Orthopedic Management[edit | edit source]

  • Spinal deformities
    • Scoliosis
      • Bracing
        • Limit scoliosis progression during growth years, not corrective
      • Surgical intervention (hardware implantation)
        • The goal is to ultimately promote better breathing mechanics and sitting alignment [12]
  • Contractures
    • Management through Physical Therapy
    • Surgical intervention if significant impairment or pain is present
  • Fractures
    • Cast immobilization if non-ambulatory
    • Surgical fixation, if ambulatory

Nutrition Management[edit | edit source]

  • Maintenance of adequate nutritional intake
    • Adequate calcium and vitamin D
  • Maintenance of appropriate body mass index
  • Screening and monitoring for complications such as...
    • Glucose abnormalities
    • Hyperlipidemia
    • Abnormal fatty acid metabolism
    • Metabolic acidosis [12]

Speech and Language Pathology[edit | edit source]

  • Screening and intervention for dysphagia

Medical Management[13]:

  • Neuroprotective drugs like riluzole
  • Drugs to improve energy metabolism
  • Drugs affecting the gene expression of SMN. [12]

Gene Therapy:[edit | edit source]

  • Along with advances in medical management, gene therapy approaches have been evaluated for SMA, using viral vectors to replace the SMN1 gene.[14]

Physiotherapy[edit | edit source]

  • Merconi et al.[12] provide a comprehensive outline of physiotherapy management for SMA broken down by functional level.
Table derived from Merconi et al.[12]
Functional Level Goals Possible Deficits Possible Interventions/Adaptations
Patients not able to sit unsupported
  • Facilitate optimal function
  • Deficiencies in postural control
  • Decreased sitting tolerance
  • Contractures
  • Muscular weakness
  • Thoracic and cervical bracing to promote appropriate positioning and posture
  • Orthoses, splints, serial casting, AAROM, PROM, stretching, and or standing frame use to facilitate contracture prevention and management
  • Adaptive equipment
    • Sitting brace or sitting system
    • Postural support equipment
    • Positioning equipment
    • Hoist or lift system
    • Recline/tilt wheelchair
  • Eye tracking equipment for communication and computer use
Patients able to sit unsupported
  • Contracture management/prevention
  • Scoliosis management/prevention
  • Facilitate independence with function and mobility
  • Deficiencies in postural control
  • Contractures
  • Muscle weakness
  • Thoracic and cervical bracing to promote appropriate posture
  • Orthoses, splints, serial casting, AAROM, PROM, stretching, and or standing frame use to facilitate contracture prevention and management
  • Adaptive equipment
    • If needed, any equipment suggested for patients not able to sit unsupported
    • Gait training devices
    • UE support devices
    • Power or lightweight wheelchair with appropriate postural support
Patients able to ambulate
  • Facilitate highest level of function
  • Improve or maintain joint ROM/contracture management and or prevention
  • Improve of maintain endurance
  • Improve or maintain balance
  • Deficiencies in postural control
  • Contractures
  • Muscle weakness
  • Decreased endurance
  • Decreased balance
  • Thoracic and cervical bracing to promote appropriate posture (while in sitting)
  • Orthoses, splints, serial casting, AAROM, PROM, stretching, and or standing frame use to facilitate contracture prevention and management
  • Adaptive equipment
    • If needed, any equipment suggested for patients not able to sit unsupported
    • Power wheelchair, lightweight wheelchair, or scooter for longer distances
  • Gait training for improvement of endurance, efficiency, and safety
  • Balance training

Respiratory Care[edit | edit source]

Many children and adults with Spinal muscular atrophy will be dependent on pulmonary management due to a loss of muscle function. A respiratory therapist should be included in the multidisciplinary treatment team from an early stage to ensure proper respiratory management.[15]

  • Chest physiotherapy - assists with respiratory management and should be one of the primary airway clearance therapies.[15]
  • Mechanical insufflation–exsufflation - devices such as Cough Assist or Vit alCough can be used and this should be one of the primary airway clearance therapies.[15]
  • Suctioning is a critical part of the treatment and should be used in all patients with excessive secretions or in those with an ineffective cough.
  • The high-frequency chest wall oscillation (Vest) is another option for managing secretions. However, there is no evidence that the Vest improves airway clearance or secretions.[15]
  • Non-invasive positive pressure ventilation (NIV) should be used for respiratory failure or to prevent chest wall distortion.[15]
  • Continuous positive airway pressure (CPAP) should be used only when NIV is not tolerated or in the treatment of chronic respiratory failure.[15]

References[edit | edit source]

  1. 1.0 1.1 1.2 Darras BT, Markowitz JA, Monani UR, De Vivo DC. Spinal muscular atrophies (2015) Neuromuscular Disorders of Infancy. Childhood, and Adolescence: A Clinician’s Approach.:117-45.
  2. 2.0 2.1 2.2 Ramsey D, Scoto M, Mayhew A, Main M, Mazzone ES, Montes J, de Sanctis R, Dunaway Young S, Salazar R, Glanzman AM, Pasternak A. Revised Hammersmith Scale for spinal muscular atrophy: A SMA specific clinical outcome assessment tool. PloS one. 2017 Feb 21;12(2):e0172346.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 Umphrend D, Lazaro R, Roller M, Burton G. Umphrend's Neurological Rehabilitation. Sixth Edition. St. Louis, MO, USA. Elsevier Mosby, 2013.
  4. Genentech. Understanding Spinal Muscular Atrophy (SMA). Available from: https://www.youtube.com/watch?v=5mI_ZsWkkc4 (last accessed 7.6.2019)
  5. National Health Service. Spinal muscular atrophy. Available from https://www.nhs.uk/conditions/spinal-muscular-atrophy-sma/ Last accessed 4/24/2023.
  6. Cure SMA. Learn to Spot the Warning Signs of SMA – Snapshot of Hallmark Symptoms (Video 9) Available from: https://www.youtube.com/watch?v=G5yIdH0yans&feature=emb_logo [last accessed 31/01/2021]
  7. National Institute of Neurological Disorders and Stroke. Spinal Muscle Atrophy. Available from https://www.ninds.nih.gov/health-information/disorders/spinal-muscular-atrophy (accessed 4/26/2023).
  8. Prior TW, Leach ME, Finanger E. Table 5. [Disorders to Consider in the Differential Diagnosis of Spinal Muscular Atrophy (SMA)]. [Internet]. Nih.gov. University of Washington, Seattle; 2020 [cited 2024 Feb 6]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1352/table/sma.T.disorders_to_consider_in_the_diffe/ ‌
  9. Montes J, McDermott MP, Martens WB, Dunaway S, Glanzman AM, Riley S, Quigley J, Montgomery MJ, Sproule D, Tawil R, Chung WK. Six-Minute Walk Test demonstrates motor fatigue in spinal muscular atrophy. Neurology. 2010 Mar 9;74(10):833-8.
  10. Wijnhoven TM, de Onis M, Onyango AW, Wang T, Bjoerneboe GE, Bhandari N, Lartey A, Rashidi BA. Assessment of gross motor development in the WHO Multicentre Growth Reference Study. Food and nutrition bulletin. 2004;25(1_suppl_1):S37-45.
  11. Mazzone ES, Mayhew A, Montes J, Ramsey D, Fanelli L, Young SD, Salazar R, De Sanctis R, Pasternak A, Glanzman A, Coratti G. Revised upper limb module for spinal muscular atrophy: development of a new module. Muscle & nerve. 2017 Jun;55(6):869-74.
  12. 12.0 12.1 12.2 12.3 12.4 12.5 Mercuri E, Finkel RS, Muntoni F, Wirth B, Montes J, Main M, Mazzone ES, Vitale M, Snyder B, Quijano-Roy S, Bertini E. Diagnosis and management of spinal muscular atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscular Disorders. 2018 Feb 1;28(2):103-15.
  13. Tiziano FD, Lomastro R, Pinto AM, Messina S, D'Amico A, Fiori S, Angelozzi C, Pane M, Mercuri E, Bertini E, Neri G. Salbutamol increases survival motor neuron (SMN) transcript levels in leucocytes of spinal muscular atrophy (SMA) patients: relevance for clinical trial design. Journal of medical genetics. 2010 Dec 1;47(12):856-8.
  14. Passini MA, Cheng SH. Prospects for the gene therapy of spinal muscular atrophy. Trends in molecular medicine. 2011 May 1;17(5):259-65.
  15. 15.0 15.1 15.2 15.3 15.4 15.5 Finkel RS, Mercuri E, Meyer OH, Simonds AK, Schroth MK, Graham RJ, Kirschner J, Iannaccone ST, Crawford TO, Woods S, Muntoni F. Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics. Neuromuscular Disorders. 2018 Mar 1;28(3):197-207.