The Journal of Pediatrics
Volume 150, Issue 5 , Pages 456-457, May 2007

Muscle Memory

  • Susan T. Iannaccone, MD, FAAN

      Affiliations

    • Corresponding Author InformationReprint requests: Susan T. Iannaccone, MD, FAAN, Jimmy Elizabeth Westcott Distinguished Chair in Pediatric Neurology, Professor of Neurology and Pediatrics, University of Texas Southwestern Medical Center, Director of Child Neurology, Children’s Medical Center, 2350 Stemmons Freeway, Dallas TX 75235.

Director of Child Neurology, Children’s Medical Center, University of Texas Southwestern Medical Center, Dallas, TX

Article Outline

Abbreviations: BMD, Becker muscular dystrophy, DMD, Duchenne muscular dystrophy

 

In this issue of The Journal, Cyrulnik et al report that patients with Duchenne muscular dystrophy (DMD) often have delayed milestones, both language and motor.1 This is the first systematic study of a large cohort of patients to document that early delay does occur and can be correlated with later cognitive function.

See related article, p 474

The year 2006 marked the 20th anniversary of the discovery of the dystrophin gene and mutations that cause DMD and the allelic disorder, Becker muscular dystrophy (BMD).2, 3 In the 2 decades since, we have seen molecular explanations for facts we knew but didn’t understand, such as holes in the sarcolemma visible at the electron microscopic level. We have also learned some new things, such as there are many patients with BMD who have no weakness, but present with other manifestations such as cardiomyopathy or autism.4, 5 This knowledge has reinforced a concept that, although progressive muscle weakness is the hallmark of DMD/BMD, it is a multi-system disease.

Although the association between DMD/BMD and cognitive deficits was recognized in the earliest clinical descriptions, the role that dystrophin deficiency might play in brain dysfunction remains a mystery. Debate in the 1970s centered on whether the cognitive deficit was progressive and somehow related to loss of mobility and socialization; we now know this is not true (Hinton; personal communication). Studies of brain structure yielded little information, but positron emission tomography studies suggested a relationship between glucose utilization and dystrophin deficiency in the cerebellum.6 Few studies focused on the specifics of clinical brain dysfunction in DMD/BMD.

However, the cognitive deficits seen in DMD/BMD are not seen in other neuromuscular disorders. Spinal muscular atrophy, another common cause of weakness in infancy and childhood, is associated with excellent higher cortical function and often advanced language development.7 Likewise, children with various forms of congenital myopathies tend to perform extremely well academically.

Cyrulnik et al previously showed that DMD is associated with significant deficits in verbal memory that can explain poor school performance.8 Now, as part of their large and ambitious study of cognitive function in DMD, they have focused in this report on developmental milestones. Most neuromuscular specialists who care for patients with DMD know empirically that boys who are affected often have a history of delayed milestones and, in particular, language delay. However, many families experience inappropriate diagnosis and management because of failure to recognize the presence of the muscular abnormality before they get to the neuromuscular specialist. It is very important that pediatricians be aware that DMD is a common cause of developmental delay and school failure in the absence of or before the development of weakness. Serum creatine kinase levels should be included in the first screening tests for boys with developmental delay; creatine kinase screening is a cheap and quick test that will always have abnormal results in DMD/BMD during the first decade of life. Moreover, newborn screening and early diagnosis might make it possible to enroll young affected boys in early childhood intervention and appropriate classroom placement by age 3 years.

Although treatment with prednisone has been very effective in slowing the progression of weakness and preventing some of the medical complications of DMD, steroids may disrupt school performance by causing decreased attention span and irritability.9 The authors of the report by Cyrulnik et al do not mention whether any of their patients were taking steroids at the time of neuropsychological testing. It is clear from their work that the search for new treatments as effective as prednisone should include a consideration for effects on cognitive function, especially verbal memory.

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References 

  1. Cyrulnik SE, Fee RJ, De Vivo DC, Goldstein E, Hinton VJ. Delayed developmental language milestones in children with Duchenne muscular dystrophy. J Pediatr. 2007;150:474–478
  2. Kunkel LM, Hejtmancik JF, Caskey CT, Speer A, Monaco AP, Middlesworth W, et al. Analysis of deletions in DNA from patients with Becker and Duchenne muscular dystrophy. Nature. 1986;322:73–77
  3. Rowland LP. Dystrophin: a triumph of reverse genetics and the end of the beginning. N Engl J Med. 1988;318:1392–1394
  4. North KN, Miller G, Iannaccone ST, Clemens PR, Chad DA, Bella I, et al. Cognitive dysfunction as the major presenting feature of Becker’s muscular dystrophy. Neurology. 1996;46:461–465
  5. Wu JY, Kuban KC, Allred E, Shapiro F, Darras BT. Association of Duchenne muscular dystrophy with autism spectrum disorder. J Child Neurol. 2005;20:790–795
  6. Lee JS, Pfund Z, Juhasz C, Behen ME, Muzik O, Chugani DC, et al. Altered regional brain glucose metabolism in Duchenne muscular dystrophy: a pet study. Muscle Nerve. 2002;26:506–512
  7. von Gontard W, Zerres K, Backes M, Laufersweiler-Plass C, Wendland C, Melchers P, et al. Intelligence and cognitive function in children and adolescents with spinal muscular atrophy. Neuromuscul Disord. 2002;12:130–136
  8. Hinton VJ, De Vivo DC, Nereo NE, Goldstein E, Stern Y. Poor verbal working memory across intellectual level in boys with Duchenne dystrophy. Neurology. 2000;54:2127–2132
  9. Wong BL, Christopher C. Corticosteroids in Duchenne muscular dystrophy: a reappraisal. J Child Neurol. 2002;17:183–190

PII: S0022-3476(07)00174-6

doi:10.1016/j.jpeds.2007.02.056

Refers to article:

  • Delayed Developmental Language Milestones in Children with Duchenne’s Muscular Dystrophy

    Shana E. Cyrulnik, Robert J. Fee, Darryl C. De Vivo, Edward Goldstein, Veronica J. Hinton
    The Journal of Pediatrics May 2007 (Vol. 150, Issue 5, Pages 474-478)

The Journal of Pediatrics
Volume 150, Issue 5 , Pages 456-457, May 2007

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