eMedicine Specialties > Physical Medicine and Rehabilitation > Disorders of the Motor Unit

Kugelberg Welander Spinal Muscular Atrophy: Differential Diagnoses & Workup

Author: Joyce L Oleszek, MD, Assistant Professor, Department of Physical Medicine and Rehabilitation, University of Colorado at Denver Health Sciences Center, The Children's Hospital of Denver
Coauthor(s): Stephanie E Vallee, MS, Certified Genetic Counselor, Dartmouth-Hitchcock Medical Center, Children's Hospital at Dartmouth; Michael Dichiaro, MD, Chief Resident, Department of Physical Medicine and Rehabilitation, University of Colorado at Denver Health Sciences Center; Mary Louise Caire, MD, Consulting Staff, Department of Physical Medicine and Rehabilitation, Wise Regional Medical Center; Stephen Kishner, MD, Residency Program Director, Professor of Clinical Medicine, Department of Medicine, Section of Physical Medicine and Rehabilitation, Louisiana State University School of Medicine
Contributor Information and Disclosures

Updated: Jul 29, 2008

Differential Diagnoses

Amyotrophic Lateral Sclerosis
Myasthenia Gravis
Becker Muscular Dystrophy
Paraneoplastic Encephalomyelitis
Botulism
Poliomyelitis
Carnitine Deficiency
Polymyositis
Dermatomyositis
Lambert-Eaton Myasthenic Syndrome
Malnutrition

Other Problems to Be Considered

Duchenne muscular dystrophy
Glycolytic or lipid storage myopathy
Polyneuritis
Endocrine-related myopathy
Muscular hypotonia secondary to Marfan syndrome or Prader-Willi syndrome
Malnutrition
Metabolic disorders (eg, organic aciduria) and mitochondrial disorders
Leukodystrophy
Peripheral neuropathies
Transverse myelitis
Arthrogryposis multiplex congenita
Hodgkin disease associated anterior horn disease
Macroglobulinemia associated anterior horn disease

Workup

Laboratory Studies

  • Molecular genetic testing12,13  - Routine diagnostic testing for spinal muscular atrophy (SMA) involves targeted mutation analysis to detect deletion of exons 7 and 8 of SMN1. Approximately 95-98% of individuals with a clinical diagnosis of SMA lack exon 7 in both copies of SMN1 (ie, they are homozygous for the deletion). Approximately 2-5% of individuals with a clinical diagnosis of SMA are compound heterozygotes for deletion of SMN1 exon 7 and an intragenic mutation of SMN1. Routine genetic testing detects only patients with the homozygous deletion. However, additional testing is available that includes SMN1 sequence analysis for the detection of point mutations in the SMN1 gene. Genetic testing has also been developed that uses the quantitative polymerase chain reaction to determine the SMN2 gene copy number; however, such testing is not yet widely available. The SMN2 gene copy number is variable, rangingfrom0-5.
  • Other testing - Serum creatine kinase levels may be elevated, but usually not to the extent that they are elevated in persons with muscular dystrophy. Serum aldolase levels also are commonly elevated in persons with types III and IV SMA.

Imaging Studies

  • Ultrasonographic imaging of the muscles has been used to assess for neurogenic atrophy in spinal muscular atrophy (SMA), but it is fairly nonspecific. Ultrasonography has lost favor as a diagnostic tool for SMA. Neuroimaging of patients with SMA reveals no brain abnormalities.

Other Tests

  • Muscle biopsy reveals evidence of neurogenic atrophy and chronic reinnervation in spinal muscular atrophy (SMA). Skeletal muscle changes include atrophy with a combination of narrow fibers and large, hypertrophic fibers. These fibers are separated by abundant fat and fibrous tissues. Increase in the sarcolemmal nuclei with preservation of striations is observed. The phrenic (C3-C5) and sacral (S2-S4) sphincter motor neurons are spared. Typical findings consistent with neurogenic atrophy also are seen on biopsy and are discussed above in the Pathophysiology section.
  • Electromyography (EMG) and nerve conduction studies (NCS) can be very useful for the physician in the diagnosis of SMA. Diffuse abnormalities on EMG are seen in the extremities and bulbar musculature. The findings are consistent with axonal degeneration. Fibrillation potentials, positive sharp waves, and complex, repetitive discharges are common. Large motor unit potentials are typical, but small amplitudes also have been seen. Upon recruitment, polyphasic motor unit potentials, decreased recruitment, fast firing, and synchronization of motor units are seen. A marked increase in jitter on electromyograms often is seen and helps to differentiate SMA types III and IV from ALS. Motor nerve conduction velocities are normal or slightly decreased. Motor unit action potentials (MUAPs) progressively decrease in amplitude. Sensory nerve action potentials (SNAPs) are normal.

More on Kugelberg Welander Spinal Muscular Atrophy

Overview: Kugelberg Welander Spinal Muscular Atrophy
Differential Diagnoses & Workup: Kugelberg Welander Spinal Muscular Atrophy
Treatment & Medication: Kugelberg Welander Spinal Muscular Atrophy
Follow-up: Kugelberg Welander Spinal Muscular Atrophy
References
[ CLOSE WINDOW ]

References

  1. Bradley WG, ed. Neurology in Clinical Practice. 5th ed. Philadelphia, Pa: Butterworth-Heinemann/Elsevier; 2008.

  2. Herring JA, ed. Tachdjian's Pediatric Orthopaedics. 4th ed. Philadelphia, Pa: Saunders/Elsevier; 2008.

  3. Wang CH, Finkel RS, Bertini ES, et al. Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol. Aug 2007;22(8):1027-49. [Medline].

  4. Russman BS, Buncher CR, White M, et al. Function changes in spinal muscular atrophy II and III. The DCN/SMA Group. Neurology. Oct 1996;47(4):973-6. [Medline].

  5. Zerres K, Rudnik-Schöneborn S, Forrest E, et al. A collaborative study on the natural history of childhood and juvenile onset proximal spinal muscular atrophy (type II and III SMA): 569 patients. J Neurol Sci. Feb 27 1997;146(1):67-72. [Medline].

  6. Ioos C, Leclair-Richard D, Mrad S, et al. Respiratory capacity course in patients with infantile spinal muscular atrophy. Chest. Sep 2004;126(3):831-7. [Medline]. [Full Text].

  7. Lin LC, Jong YJ. Pulmonary function assessment in patients with spinal muscular atrophy type II and type III. Acta Paediatr Taiwan. Jan-Feb 2004;45(1):15-8. [Medline].

  8. Muscular Dystrophy Campaign sponsored workshop: recommendation for respiratory care of children with SMA type II and III. Neuromuscular Disord. 2003;13:184-189.

  9. Moosa A, Dubowitz V. Spinal muscular atrophy in childhood. Two clues to clinical diagnosis. Arch Dis Child. May 1973;48(5):386-8. [Medline]. [Full Text].

  10. Simic G. Pathogenesis of proximal autosomal recessive spinal muscular atrophy. Acta Neuropathol. Jul 16 2008;[Medline].

  11. Mattis VB, Bowerman M, Kothary R, et al. A SMNDelta7 read-through product confers functionality to the SMNDelta7 protein. Neurosci Lett. Jun 26 2008;[Medline].

  12. Ogino S, Wilson RB. Genetic testing and risk assessment for spinal muscular atrophy (SMA). Hum Genet. Dec 2002;111(6):477-500. [Medline].

  13. Wang CC, Chang JG, Ferrance J, et al. Quantification of SMN1 and SMN2 genes by capillary electrophoresis for diagnosis of spinal muscular atrophy. Electrophoresis. Jul 2008;29(13):2904-11. [Medline].

  14. Umphred DA, ed. Neurological Rehabilitation. 5th ed. St Louis, Mo: Mosby Elsevier; 2007.

  15. Rodillo E, Marini ML, Heckmatt JZ, et al. Scoliosis in spinal muscular atrophy: review of 63 cases. J Child Neurol. Apr 1989;4(2):118-23. [Medline].

  16. Puruckherr M, Mehta JB, Girish MR, et al. Severe obstructive sleep apnea in a patient with spinal muscle atrophy. Chest. Nov 2004;126(5):1705-7. [Medline]. [Full Text].

  17. Yasuma F, Kuru S, Konagaya M. Dilated cardiomyopathy in Kugelberg-Welander disease: coexisting sleep disordered breathing and its treatment with continuous positive airway pressure. Intern Med. Oct 2004;43(10):951-4. [Medline]. [Full Text].

  18. Merlini L, Granata C, Bonfiglioli S, et al. Scoliosis in spinal muscular atrophy: natural history and management. Dev Med Child Neurol. Aug 1989;31(4):501-8. [Medline].

  19. Swoboda KJ, Kissel JT, Crawford TO, et al. Perspectives on clinical trials in spinal muscular atrophy. J Child Neurol. Aug 2007;22(8):957-66. [Medline].

  20. Il'ina NA, Antipova RI, Khokhlov AP. [Use of lithium carbonate to treat Kugelberg--Welander spinal amyotrophy]. Zh Nevropatol Psikhiatr Im S S Korsakova. 1980;80(11):1657-60. [Medline].

  21. Tzeng AC, Cheng J, Fryczynski H, et al. A study of thyrotropin-releasing hormone for the treatment of spinal muscular atrophy: a preliminary report. Am J Phys Med Rehabil. Sep-Oct 2000;79(5):435-40. [Medline].

  22. Merlini L, Solari A, Vita G, et al. Role of gabapentin in spinal muscular atrophy: results of a multicenter, randomized Italian study. J Child Neurol. Aug 2003;18(8):537-41. [Medline].

  23. de Groot IJ, de Witte LP. Physical complaints in ageing persons with spinal muscular atrophy. J Rehabil Med. Jul 2005;37(4):258-62. [Medline].

  24. Liveson JA. Peripheral Neurology: Case Studies in Electrodiagnosis. 2nd ed. Philadelphia, Pa: FA Davis; 1991.

  25. Menkes JH. Textbook of Child Neurology. 5th ed. Baltimore, Md: Williams & Wilkins; 1995.

  26. Swaiman KF, Ashwal S, Ferriero DM, eds. Pediatric Neurology: Principles and Practice. 4th ed. Philadelphia, Pa: Mosby; 2006.

  27. Ropper AH, Brown RH. Adams and Victor's Principles of Neurology. 8th ed. New York, NY: McGraw-Hill Medical; 2005.

  28. Younger DS, Gordon PH. Diagnosis in neuromuscular diseases. Neurol Clin. Feb 1 1996;14:135-68.

  29. Zeinos M, Sampath J, Cole C, et al. Operative treatment for hip subluxations in spinal muscular atrophy. J Bone Joint Surg. 2005;87-B:1541-4.

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

Kugelberg Welander spinal muscular atrophy, Kugelberg-Welander spinal muscular atrophy, Kugelberg Welander disease, Kugelberg-Welander disease, Wohlfart-Kugelberg-Welander syndrome, Wohlfart-Kugelberg-Welander disease, mild spinal muscular atrophy, spinal muscular atrophy, SMA, juvenile types III and IV spinal muscular atrophy, adult-onset spinal muscular atrophy

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Joyce L Oleszek, MD, Assistant Professor, Department of Physical Medicine and Rehabilitation, University of Colorado at Denver Health Sciences Center, The Children's Hospital of Denver
Joyce L Oleszek, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation
Disclosure: Nothing to disclose.

Coauthor(s)

Stephanie E Vallee, MS, Certified Genetic Counselor, Dartmouth-Hitchcock Medical Center, Children's Hospital at Dartmouth
Disclosure: Nothing to disclose.

Michael Dichiaro, MD, Chief Resident, Department of Physical Medicine and Rehabilitation, University of Colorado at Denver Health Sciences Center
Disclosure: Nothing to disclose.

Mary Louise Caire, MD, Consulting Staff, Department of Physical Medicine and Rehabilitation, Wise Regional Medical Center
Mary Louise Caire, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Stephen Kishner, MD, Residency Program Director, Professor of Clinical Medicine, Department of Medicine, Section of Physical Medicine and Rehabilitation, Louisiana State University School of Medicine
Stephen Kishner, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation and American Association of Neuromuscular and Electrodiagnostic Medicine
Disclosure: Nothing to disclose.

Medical Editor

Teresa L Massagli, MD, Residency Director, Professor, Department of Rehabilitation Medicine and Pediatrics, University of Washington School of Medicine
Teresa L Massagli, MD is a member of the following medical societies: American Academy of Pediatrics, American Academy of Physical Medicine and Rehabilitation, and Association of Academic Physiatrists
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Kat Kolaski, MD, Assistant Professor, Departments of Orthopedic Surgery and Pediatrics, Wake Forest University School of Medicine
Kat Kolaski, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine and American Academy of Physical Medicine and Rehabilitation
Disclosure: Nothing to disclose.

CME Editor

Kelly L Allen, MD, Consulting Staff, Department of Physical Medicine and Rehabilitation, Lourdes Regional Rehabilitation Center, Our Lady of Lourdes Medical Center
Disclosure: Nothing to disclose.

Chief Editor

Denise I Campagnolo, MD, MS, Director of Multiple Sclerosis Clinical Research and Staff Physiatrist, Barrow Neurology Clinics, St. Joseph's Hospital and Medical Center; Investigator for Barrow Neurology Clinics; Director, NARCOMS Project for Consort
Denise I Campagnolo, MD, MS is a member of the following medical societies: Alpha Omega Alpha, American Association of Neuromuscular and Electrodiagnostic Medicine, American Paraplegia Society, Association of Academic Physiatrists, and Consortium of Multiple Sclerosis Centers
Disclosure: Teva Neuroscience Honoraria Speaking and teaching; Serono-Pfizer Honoraria Speaking and teaching

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.