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A Systematic Approach to Myopathy

This week in Morning Report, one of our AACU colleagues presented the case of a patient with new onset muscle weakness, intermittent difficulty with fine motor control, and evidence of CK elevation on bloodwork. Although the exact diagnosis is still unclear, the history and physical exam were concerning for possible myopathy, or disorder of muscle structure/function.

‘Weakness’ is a very common presentation in primary care and general internal medicine, and seeing that word on a referral sheet is often the cause of some consternation because the list of possible diagnoses is so broad! So…let’s go through a comprehensive, systematic approach to muscle weakness.

Myopathy = disorder of (usually skeletal) muscle. Image from Wikimedia Commons

1. First, differentiate between muscle weakness vs. non-muscle weakness

Patients who are feeling weak may not be able to articulate exactly how or where they are weak, and may perceive fatigue, somnolence, lack of energy, or functional impairment as weakness. This is where your history-taking and careful examination of motor strength are key!

  • Your first branching point is to identify true muscle weakness (i.e., limitation of motor strength as graded on the MRC scale) vs. non-muscle reasons for generalized weakness (e.g., fatigue, anemia, dyspnea due to various causes, cachexia, depression). Carefully characterize the pattern of weakness (unilateral vs. bilateral, proximal vs. distal muscles) as well as associated neurological symptoms (upper motor vs. lower motor neuron signs)
  • Remember that myopathy refers to some disorder of skeletal muscle itself (be it with the muscle structure, channels, etc.). This means that the ‘lesion’ (conceptually speaking) localizes to the muscle unit itself, rather than the cortex, motor neuron, peripheral nerve, or neuromuscular junction. Again, a careful history and physical examination looking for ‘upstream’ signs such fatiguability, sensory deficits, bulbar signs/symptoms will help you identify where along the brain-to-muscle pathway the defect lies.

The following figure from Barohn et al.’s pattern-based review paper on myopathies contains a useful head-to-toe list of symptoms to ask your patients about. In particular, eliciting proximal vs. distal muscle weakness is very clinically high-yield: ask about difficulty getting up from a chair, reaching overhead cupboards (proximal weakness) vs. turning the key in the ignition or opening jars (distal weakness).

Functional assessment of muscle weakness, by Barohn et al., ‘A Patten Recognition Approach to the Patient with A Suspected Myopathy’, Neurol Clin. 2014 August ; 32(3): 569–vii.

2. Remember a few temporal and symptom-related pearls

  • The time of onset of myopathy, and its temporal course, are key diagnostic clues! For example, there is a long list of congenital and childhood myopathies and myotonic dystrophies (mostly familiar to our Pediatrics and Genetics colleagues) that are easy to identify based on early age of onset. In contrast, adult-onset myopathies tend to be acquired due to drugs/toxins, autoimmune/inflammatory conditions, infections, or endocrinopathies
  • Muscle pain with weakness is a clue pointing you towards toxin/drug-induced myopathies or infectious myopathies
  • Myalgias, muscle contractures, muscle stiffness/difficulty relaxing muscles, and myoglobinuria are key clues pointing you towards a host of inherited and acquired myopathies
  • Myositis simply refers to inflammation of the muscle body, classically seen in inflammatory conditions such as polymyositis, dermatomyositis, and inclusion body myositis. PM/DM typically present with proximal muscle weakness, whereas mixed proximal/distal weakness +/- bulbar symptoms should raise suspicion for inclusion body myositis, which has a poorer response to treatment. Note: our understanding of inflammatory myositis is evolving very rapidly — we have now identified many, many more myositis antibodies than ever before, and there is increasing recognition that myositis is a heterogeneous umbrella of diseases rather than just the 3 big ones named above.

3. Remember the following basic ‘buckets’ for organizing your differential diagnosis for myopathies

Here I go with the buckets again! The image below summarizes how I categorize myopathies in my head without having to remember long lists. This is not an exhaustive list by any means, but is a great scaffolding upon which you can build a clinical impression guided by your investigations.

4. Remember the following useful investigations

In addition to routine bloodwork, we typically order:

  • CK – see wide list of conditions below in which CK may be elevated
  • Liver enzymes
  • TSH
  • ESR/CRP
  • +/- ANA, RF
  • +/- Myositis panel (checking for autoantibodies — usually sent by our Rheum colleagues)
  • anti-HMGCR if suspicious of statin-induced myopathy
  • +/- EMG
  • +/- Muscle biopsy if concerned about inflammatory myositis
  • +/- MRI myositis protocol if concerned about inflammatory myositis
  • Genetic testing if concerned about inherited myopathy

Some myopathies are associated with cardiac and respiratory manifestations, so it’s important to refer these patients to the appropriate subspecialists expeditiously, and to consider appropriate testing (e.g., Echocardiogram, MIPS/MEPS/FVC/diaphragmatic studies) as needed.

A basic differential diagnosis for CK elevation, adapted from Barohn et al., A Patten Recognition Approach to the Patient with A Suspected Myopathy’, Neurol Clin. 2014 August ; 32(3): 569–vii.

Many thanks to our AACU colleague for bringing a case that generated some valuable learning points. I hope you found this Morning Report useful!

Note: These recaps are based on real-life cases presented during weekly Morning Report; however, no real patient findings/investigations/images/identifying details are used. Any clinical information presented has been modified and completely de-identified for privacy.

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