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Spinal muscular atrophy

Spinal Muscular Atrophy (SMA) is a term applied to a number of different disorders, all having in common a genetic cause and the manifestation of weakness due to loss of the motor neurons of the spinal cord and brainstem. more...

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Shwachman syndrome
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Sickle-cell disease
Silver-Russell dwarfism
Sipple syndrome
Sjogren's syndrome
Sly syndrome
Smith-Magenis Syndrome
Soft tissue sarcoma
Sotos syndrome
Spasmodic dysphonia
Spasmodic torticollis
Spinal cord injury
Spinal muscular atrophy
Spinal shock
Spinal stenosis
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Splenic-flexure syndrome
Squamous cell carcinoma
St. Anthony's fire
Stein-Leventhal syndrome
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Caused by mutation of the SMN gene

The most common form of SMA is caused by mutation of the SMN gene, and manifests over a wide range of severity affecting infants through adults. This spectrum has been divided arbitrarily into three groups by the level of weakness.

  • Infantile SMA - Type 1 or Werdnig-Hoffmann disease (generally 0-6 months). SMA type 1, also known as severe infantile SMA or Werdnig Hoffmann disease, is the most severe, and manifests in the first year of life with the inability to ever maintain an independent sitting position.
  • Intermediate SMA - Type 2 (generally 7-18 months). Type 2 SMA, or intermediate SMA, describes those children who are never able to stand and walk, but who are able to maintain a sitting position at least some time in their life. The onset of weakness is usually recognized some time between 6 and 18 months.
  • Juvenile SMA - Type 3 Kugelberg-Welander disease (generally >18 months). SMA type 3 describes those who are able to walk at some time. It is also known as Kugelberg Welander disease.

Other forms of SMA

Other forms of spinal muscular atrophy are caused by mutation of other genes, some known and others not yet defined. All forms of SMA have in common weakness caused by denervation, i.e. the muscle atrophies because it has lost the signal to contract due to loss of the innervating nerve. Spinal muscular atrophy only affects motor nerves. Heritable disorders that cause both weakness due to motor denervation along with sensory impairment due to sensory denervation are known by the inclusive label Charcot-Marie-Tooth or Hereditary Motor Sensory Neuropathy. The term spinal muscular atrophy thus refers to atrophy of muscles due to loss of motor neurons within the spinal cord.

  • Hereditary Bulbo-Spinal SMA Kennedy's disease (X linked, Androgen receptor)
  • Spinal Muscular Atrophy with Respiratory Distress (SMARD 1) (chromsome 11, IGHMBP2 gene)
  • Distal SMA with upper limb predominance (chromosome 7, glycyl tRNA synthase)


The course of SMA is directly related to the severity of weakness. Infants with the severe form of SMA frequently succumb to respiratory disease due to weakness of the muscles that support breathing. Children with milder forms of SMA naturally live much longer although they may need extensive medical support, especially those at the more severe end of the spectrum.

Although gene replacement strategies are being tested in animals, current treatment for SMA consists of prevention and management of the secondary effect of chronic motor unit loss. It is likely that gene replacement for SMA will require many more years of investigation before it can be applied to humans. Due to molecular biology, there is a better understanding of SMA. The disease is caused by deficiency of SMN (survival motor neuron) protein, and therefore approaches to developing treatment include searching for drugs that increase SMN levels, enhance residual SMN function, or compensate for its loss. The first effective specific treatment for SMA may be only a few years away, as of 2005.


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There are other ways to manage spinal muscular atrophy type 1
From CHEST, 4/1/05 by John R. Bach

To the Editor:

The authors of a recent article in CHEST (September 2004) (1) described their management outcomes for patients with infantile spinal muscle atrophy (SMA) without comparing them to other studies. First, the system they used for classifying SMA, that is, by age of onset, has been largely abandoned because of its inherent inconsistencies in favor of stratification by disease severity. A more widely accepted classification is as follows: type 1, children who can never sit; type 2, children who can sit but not stand; and type 3, children who can walk. The authors" type 3 is "for onset after the age of walking"; however, it is not uncommon for these children to be symptomatic in infancy but then never sit or walk, sit, or even begin walking at age 3 years. Indeed, while SMA is a continuum of pathology, "age at onset" is more a reflection on the astuteness of the observer than of disease severity. Their "intermediate type 1" patients who can "raise their heads," many of whom, no doubt, can sit, would be classified as being type 2 by the majority of clinicians today. This is important because their "type 1 intermediates," shown in Figure 1 of their article, have vital capacities (VCs) as high as 75% of normal. In our 112 children with type 1 SMA, who could never sit, and who developed respiratory failure and the need for gastrostomy tubes before their second birthdays, the average maximum VC ever attained was 142 mL. The VC did not increase with age, and the high value at any time (to age 11 years) for any patient was 300 mL, or about 10% of normal values. Thus, the typical children with type 1 SMA who we described correspond to the "true type 1s," patients who the authors reported invariably had died or had undergone tracheotomy.

The most unfortunate aspect of this long-tern1 retrospective experience of one center is that it involves conventional management approaches that date back many years. Intubated patients who could not breathe either died or underwent tracheotomy. It ignored the outcomes that we and others have obtained by the following means: (1) administering nocturnal, high-span, bilevel positive-pressure ventilation (BPPV) to patients to prevent pectus excavatum and to promote lung growth from the time of diagnosis (2); (2) extubating SMA type 1 patients, even when they were completely unable to breathe with high-span BPPV, and using mechanically assisted coughing (MAC) [via the translaryngeal tubes and via a mask postextubation] (3,4); (3) and using an oximetry/BPPV/MAC outpatient protocol to avert hospitalizations for pneumonia and respiratory failure. The placement of invasive tubes is avoided even when patients are completely unable to breathe unaided. (4) As a result of our noninvasive management, 80 of our 115 SMA type 1 patients (excluding any who first developed respiratory failure or the need for gastrostomy after 23 months of age) are still alive without tracheostomy tubes at 4 years of age, with 8 patients > 8 years of age and 2 patients > l0 years of age. Many of our patients needed to be intubated on [greater than or equal to] 10 occasions before age 5 years and, because they now are able to cooperate with the outpatient protocol, have not been hospitalized in [greater than or equal to] 5 years. Only 4 of our 115 true SMA type 1 patients have required tracheotomy for bradycardia or bronchiomalacia, but not for ventilatory support, even though all use high-span BPPV, at least when sleeping, and as many as 60 patients use it up to 24 h per day.

The failure to address outcomes was also apparent when these authors reported the use of nasal ventilation at approximately 15 to 25 cm [H.sub.2]O for 20 min two or three time per day for "good thoracic expansion" without describing outcomes. They did not mention the fact that the use of nocturnal high-span BPPV prevents pectus excavatum entirely and promotes lung growth. (2) If therapy with low-span BPPV for only 60 min a day is enough, then nocturnal BPPV may not be necessary, but this study did not address that issue.

In summary, the article by Ioos et al (1) is misleading in its declaration that the majority of SMA type 1 patients must die or undergo tracheotomy. While passive neglect to death and tracheotomy are options that have advantages and disadvantages, optimal noninvasive management with MAC and up to continuous long-term BPPV, and the recently reported extubation approaches, were not attempted or even referred to in this article. Indeed, the latter two approaches were not even mentioned.

John R. Bach, MD

UMDNJ-New Jersey Medical School

Newark, NJ

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail:

Correspondence to: John R. Bach, MD, UMDNJ-New Jersey Medical School Department of Physical Medicine and Rehabilitation, University Hospital, B-403, 150th St, Newark, NJ 07871; e-mail:


(1) Ioos C, Leclair-Richard D, Mrad S, et al. Respiratory capacity course in patients with infantile spinal muscular atrophy. Chest 2004; 126:831-837

(2) Bach JR. Prevention of pectus excavatum for children with spinal muscular atrophy type 1. Am J Phys Med Rehabil 2003; 82:815-819

(3) Bach JR, Niranjan V, Weaver B. Spinal muscular atrophy type 1: a noninvasive respiratory management approach. Chest 2000; 117:1100-1105

(4) Bach JR, Baird JS, Plosky D, et al. Spinal muscular atrophy type 1: management and outcomes. Pediatr Pulmonol 2002; 34:16-22

To the Editor:

We read with interest Dr. Bach's letter concerning our study in CHEST (September 2004). (1) For classification, we used the international classification promoted by the spinal muscular atrophy (SMA) consortium. It is the only way to carry out comparable therapeutic trials. Children with SMA "true type I" are the "floppy" children with very poor motility in early months, early brainstem lesions, and severe swallowing disturbances leading to sudden death or respiratory insufficiency, whatever the form of noninvasive treatment.

Regarding SMA "intermediate type I" patients, these children can raise their head at a normal age or later, though subsequently this ability can he lost. They have never been able to sit. So, these patients are SMA type I and not type II, as suggested by Dr. Bach. They experience respiratory failure later and benefit from early noninvasive therapies such as noninvasive nocturnal ventilation.

The aim of our report was to show the progressive worsening course of vital capacity in SMA patients, whatever the type. Management for these patients consists of respiratory physiotherapy including assisted cough, chest percussion therapy, intermittent positive-pressure ventilation for 20 min three times a day, and nasal nocturnal ventilation with a noninvasive facial mask. This management limits the risk of respiratory distress requiring invasive mechanical ventilation. Nevertheless, false passages of saliva with swallowing disturbances increase pulmonary congestion and the risk of aspiration pneumonia in SMA intermediate type I children. So, in our experience, nasal nocturnal ventilation is poorly efficacious in these SMA patients.

When an intermediate type I patient needs invasive ventilation, we maintain mechanical ventilation for 3 weeks. Then, after the tube is removed, the patient continues with nasal nocturnal ventilation and intermittent positive-pressure ventilation for 20 min three times a day. If, despite this management, the patient requires invasive ventilation more than three times during the same year or requires nasal ventilation not only during sleeping, but also while awake, a tracheostomy is performed.

Treatment has changed over the years. We agree with Dr. Bach that patients with respiratory paralysis benefit from preventive noninvasive treatment with hyperinsufflation and noninvasive nocturnal ventilation, which is associated with help in coughing. At the present time, we also use percussion therapy with respiratory physiotherapy every day at home, and these treatments delay the acute respiratory worsening.

In our experience, patients with tracheostomy tubes are no longer hospitalized until spine surgery and are less dependent on their environment. Severely affected children cannot attend a boarding school while using noninvasive ventilation. So, even now we perform a tracheostomy in ventilatory-dependent children who require daylong therapy. Dr. Bach said that "many of their patients needed to be intubated on 10 or more occasions before age 5" and that "patients ... use high span BPPV [bilevel positive pressure ventilation] at least when sleeping and as many as 60 use it up to 24 hours a day." In our opinion, for a patient who needs continuous nasal ventilation, or requires invasive ventilation more than three times during the same year, we prefer the use of tracheostomy, which allows a better quality of life. Mechanical ventilation with good thoracic expansion prevents pectus excavatum.

Christine Ioos, MD

Hopital Raymond Poincard Garches, France

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail:

Correspondence to: Christine Ioos, MD, Hopital Raymond Poincard, 104 Blvd Raymond Poincard, Garches, France 92380; e-mail:


(1) Ioos C. Leclair-Richard D, Mrad S, et al. Respiratory capacity course in patients with infantile spinal muscular atrophy. Chest 2004; 126:831-837

COPYRIGHT 2005 American College of Chest Physicians
COPYRIGHT 2005 Gale Group

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