Muscle Weakness in Adults: Evaluation and Differential Diagnosis

 

Although the prevalence of muscle weakness in the general population is uncertain, it occurs in about 5% of U.S. adults 60 years and older. Determining the cause of muscle weakness can be challenging. True muscle weakness must first be differentiated from subjective fatigue or pain-related motor impairment with normal motor strength. Muscle weakness should then be graded objectively using a formal tool such as the Medical Research Council Manual Muscle Testing scale. The differential diagnosis of true muscle weakness is extensive, including neurologic, rheumatologic, endocrine, genetic, medication- or toxin-related, and infectious etiologies. A stepwise approach to narrowing this differential diagnosis relies on the history and physical examination combined with knowledge of the potential etiologies. Frailty and sarcopenia are clinical syndromes occurring in older people that can present with generalized weakness. Asymmetric weakness is more common in neurologic conditions, whereas pain is more common in neuropathies or radiculopathies. Identifying abnormal findings, such as Chvostek sign, Babinski reflex, hoarse voice, and muscle atrophy, will narrow the possible diagnoses. Laboratory testing, including electrolyte, thyroid-stimulating hormone, and creatine kinase measurements, may also be helpful. Magnetic resonance imaging is indicated if there is concern for acute neurologic conditions, such as stroke or cauda equina syndrome, and may also guide muscle biopsy. Electromyography is indicated when certain diagnoses are being considered, such as amyotrophic lateral sclerosis, myasthenia gravis, neuropathy, and radiculopathy, and may also guide biopsy. If the etiology remains unclear, specialist consultation or muscle biopsy may be necessary to reach a diagnosis.

Given its broad differential diagnosis, muscle weakness can be challenging to evaluate in primary care practice. Although its prevalence in the general population is not well described, muscle weakness occurs in 5% of U.S. adults 60 years and older.1 Physicians must distinguish true muscle weakness from subjective fatigue or pain-related motor impairment with normal motor strength. This requires a history and physical examination, which guide laboratory testing, imaging, electrodiagnostic testing, and muscle biopsy.25

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SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingComment

History and physical examination findings should guide laboratory testing, imaging, electromyography, and muscle biopsy in patients with muscle weakness.25

C

Usual practice and expert opinion

A medication and toxin review should be completed in patients with muscle weakness.4,12,15,35

C

Usual practice and expert opinion

Electromyography should be performed in patients with muscle weakness if the diagnosis is unclear after a history, physical examination, and targeted laboratory evaluation.15,18,19,26

C

Expert opinion

Muscle biopsy should be considered to clarify the diagnosis in patients who have objective muscle weakness with elevated creatine kinase levels or abnormal findings on electromyography or muscle magnetic resonance imaging.20,21

C

Expert opinion


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingComment

History and physical examination findings should guide laboratory testing, imaging, electromyography, and muscle biopsy in patients with muscle weakness.25

C

Usual practice and expert opinion

A medication and toxin review should be completed in patients with muscle weakness.4,12,15,35

C

Usual practice and expert opinion

Electromyography should be performed in patients with muscle weakness if the diagnosis is unclear after a history, physical examination, and targeted laboratory evaluation.15,18,19,26

C

Expert opinion

Muscle biopsy should be considered to clarify the diagnosis in patients who have objective muscle weakness with elevated creatine kinase levels or abnormal findings on electromyography or muscle magnetic resonance imaging.20,21

C

Expert opinion


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.

The Authors

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SCOTT T. LARSON, MD, is a clinical assistant professor in the Department of Family Medicine at the University of Iowa Hospitals and Clinics, Iowa City....

JASON WILBUR, MD, is the director of the Geriatric Medicine Fellowship Program, associate director of the Family Medicine Residency Program, and a clinical professor in the Department of Family Medicine at the University of Iowa Carver College of Medicine, Iowa City.

Address correspondence to Jason Wilbur, MD, University of Iowa Carver College of Medicine, 200 Hawkins Dr., Iowa City, IA 52242 (email: jason-wilbur@uiowa.edu). Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.

References

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1. Looker AC, Wang CY. Prevalence of reduced muscle strength in older U.S. adults: United States, 2011–2012. January 2015. Accessed February 17, 2019. https://www.cdc.gov/nchs/products/databriefs/db179.htm...

2. Barohn RJ, Amato AA. Pattern-recognition approach to neuropathy and neuronopathy. Neurol Clin. 2013;31(2):343–361.

3. Chawla J. Stepwise approach to myopathy in systemic disease. Front Neurol. 2011;2:49.

4. Nayak R. Practical approach to the patient with acute neuromuscular weakness. World J Clin Cases. 2017;5(7):270–279.

5. Rosow LK, Amato AA. The role of electrodiagnostic testing, imaging, and muscle biopsy in the investigation of muscle disease. Continuum (Minneap Minn). 2016;22(6):1787–1802.

6. Saguil A. Evaluation of the patient with muscle weakness. Am Fam Physician. 2005;71(7):1327–1336. Accessed August 23, 2019. https://www.aafp.org/afp/2005/0401/p1327.html

7. Juel VC, Massey JM. Myasthenia gravis. Orphanet J Rare Dis. 2007;2:44.

8. Hülsbrink R, Hashemolhosseini S. Lambert-Eaton myasthenic syndrome. Clin Neurophysiol. 2014;125(12):2328–2336.

9. Dalakas MC. Inflammatory muscle diseases. N Engl J Med. 2015;372(18):1734–1747.

10. Lundberg IE, Miller FW, Tjärnlund A, et al. Diagnosis and classification of idiopathic inflammatory myopathies. J Intern Med. 2016;280(1):39–51.

11. McDonald CM. Clinical approach to the diagnostic evaluation of hereditary and acquired neuromuscular diseases. Phys Med Rehabil Clin NAm. 2012;23(3):495–563.

12. Klopstock T. Drug-induced myopathies. Curr Opin Neurol. 2008;21(5):590–595.

13. Thompson PD, Panza G, Zaleski A, et al. Statin-associated side effects. J Am Coll Cardiol. 2016;67(20):2395–2410.

14. Minetto MA, D’Angelo V, Arvat E, et al. Diagnostic work-up in steroid myopathy. Endocrine. 2018;60(2):219–223.

15. Simon L, Jolley SE, Molina PE. Alcoholic myopathy: pathophysiologic mechanisms and clinical implications. Alcohol Res. 2017;38(2):207–217.

16. Andersen H. Motor neuropathy. Handb Clin Neurol. 2014;126:81–95.

17. Iyadurai SJ, Kissel JT. The Limb-Girdle muscular dystrophies and the dystrophinopathies. Continuum (Minneap Minn). 2016;22(6, Muscle and Neuromuscular Junction Disorders):1954–1977.

18. Lacomis D. Electrodiagnostic approach to the patient with suspected myopathy. Neurol Clin. 2012;30(2):641–660.

19. Valls-Solé J. The utility of electrodiagnostic tests for the assessment of medically unexplained weakness and sensory deficit. Clin Neurophysiol Pract. 2016;1:2–8.

20. Wilson D, Breen L, Lord JM, et al. The challenges of muscle biopsy in a community based geriatric population. BMC Res Notes. 2018;11(1):830.

21. Joyce NC, Oskarsson B, Jin LW. Muscle biopsy evaluation in neuromuscular disorders. Phys Med Rehabil Clin N Am. 2012;23(3):609–631.

22. Reich DS, Lucchinetti CF, Calabresi PA. Multiple sclerosis. N Engl J Med. 2018;378(2):169–180.

23. Garg N, Park SB, Vucic S, et al. Differentiating lower motor neuron syndromes. J Neurol Neurosurg Psychiatry. 2017;88(6):474–483.

24. Tiryaki E, Horak HA. ALS and other motor neuron diseases. Continuum (Minneap Minn). 2014;20(5, Peripheral Nervous System Disorders):1185–1207.

25. Shin SC, Robinson-Papp J. Amyloid neuropathies. Mt Sinai J Med. 2012;79(6):733–748.

26. Schmidt J. Current classification and management of inflammatory myopathies. J Neuromuscul Dis. 2018;5(2):109–129.

27. Schmidt K, Schmidt J. Inclusion body myositis: advancements in diagnosis, pathomechanisms, and treatment. Curr Opin Rheumatol. 2017;29(6):632–638.

28. Callaghan BC, Cheng HT, Stables CL, et al. Diabetic neuropathy. Lancet Neurol. 2012;11(6):521–534.

29. Kumar Singh A, Kumar Maurya P, Kulshreshtha D, et al. Analysis of clinical and metabolic profile of acute neuromuscular weakness related to hypokalemia. Acta Neurol Taiwan. 2017;26(3):97–105.

30. Lana-Peixoto MA, Pedrosa D, Talim N, et al. Myelitis and cauda equina involvement following dengue fever. Mult Scler Relat Disord. 2018;20:48–50.

31. Diringer M. Neurologic manifestations of major electrolyte abnormalities. Handb Clin Neurol. 2017;141:705–713.

32. Pennisi EM, Garibaldi M, Antonini G. Lipid myopathies. J Clin Med. 2018;7(12):E472.

33. Frezza E, Terracciano C, Giacanelli M, et al. Late-onset Pompe disease with nemaline bodies. Case Rep Neurol Med. 2018:4127213.

34. Zhou SF, Xue CC, Yu XQ, et al. Clinically important drug interactions potentially involving mechanism-based inhibition of cytochrome P450 3A4 and the role of therapeutic drug monitoring. Ther Drug Monit. 2007;29(6):687–710.

35. Mammen AL. Toxic myopathies. Continuum (Minneap Minn). 2013;19(6 Muscle Disease):1634–1649.

36. Gabbai AA, Castelo A, Oliveira AS. HIV peripheral neuropathy. Handb Clin Neurol. 2013;115:515–529.

37. Hehir MK 2nd, Logigian EL. Infectious neuropathies. Continuum (Minneap Minn). 2014;20(5, Peripheral Nervous System Disorders):1274–1292.

38. Dodds R, Sayer AA. Sarcopenia and frailty: new challenges for clinical practice. Clin Med (Lond). 2015;15(suppl 6):s88–s91.

39. Liguori I, Russo G, Aran L, et al. Sarcopenia. Clin Interv Aging. 2018;13:913–927.

40. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146–M156.

41. Dimachkie MM, Barohn RJ. Distal myopathies. Neurol Clin. 2014;32(3):817–842.

42. Feinberg JH, Radecki J. Parsonage-Turner syndrome. HSS J. 2010;6(2):199–205.

43. Cooper MS, Gittoes NJ. Diagnosis and management of hypocalcaemia [published correction appears in BMJ. 2008;336(7659):10.1136/bmj.a334]. BMJ. 2008;336(7656):1298–1302.

44. Hujoel IA. The association between serum calcium levels and Chvostek sign: a population-based study. Neurol Clin Pract. 2016;6(4):321–328.

45. Naqvi U, Sherman AI. Muscle strength grading. StatPearls. Accessed February 17, 2019. https://www.ncbi.nlm.nih.gov/books/NBK430685/

46. Kim HS, Kim SM, Lee JD. Erythematous papules on dorsum of both hands. Am Fam Physician. 2017;95(12):803–804. Accessed August 26, 2019. https://www.aafp.org/afp/2017/0615/p803.html

47. Cesari M, Calvani R, Marzetti E. Frailty in older persons. Clin Geriatr Med. 2017;33(3):293–303.

48. Savva GM, Donoghue OA, Horgan F, et al. Using Timed Up-and-Go to identify frail members of the older population. J Gerontol A Biol Sci Med Sci. 2013;68(4):441–446.

 

 

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