A 69-year-old man has been ventilated for an infective exacerbation of chronic obstructive pulmonary disease (COPD). Therapy has included steroids and an aminoglycoside antibiotic. His ICU course has been complicated by septic shock and acute kidney injury.

Twelve days later neurological examination off sedation reveals moderate to severe weakness of his limbs with intact sensation, normal cognition and normal cranial nerves

  • List the differential diagnoses for his weakness.
  • Outline how you would determine the diagnosis.
  • List of differential diagnoses for his weakness

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College Answer

a) List of differential diagnoses for his weakness

    • Critical illness myopathy / Acute quadriplegic myopathy* (high dose steroids, with or without nondepolarising paralyzing agent use, Beta agonists)
  • Critical Illness polyneuropathy/myopathy* (SIRS, sepsis, MODS)
  • *Residual sedation and other drug influences (Renal [&/or liver] impairment contributing, aminoglycoside with NMJ effect)
  • *Electrolyte abnormalities (PO4, Ca++, K+)
  • Deconditioning with weakness exacerbated by subclinical sepsis
  • Underlying polyneuropathy/myopathy exacerbated by critical illness Alcohol, B12 deficiency, paraneoplastic, consider diabetic
  • GBS
  • Rhabdomyolysis (drugs (e.g. statins), infections) should be thought of given renal failure
  • acute myelitis or watershed infarction (acute upper motor neuron lesions may not yet have developed hypertonia and hyper-reflexia)
  • Autoimmune neuropathy or myopathy (rare)

b) Diagnosis

Any relevant history.

Clinical examination:

    • Normal higher functions and cranial nerves favour a critical illness neuromyopathy (CINM) or a purely peripheral nervous system. Spinal lesion possible although less likely + normal sensory examination
    • Symmetrical features on peripheral neurological exam also favours CINM. Cerebral watershed infarction is possible but less likely given distal power is usually relatively spared.
    • Critical illness myopathy often affects the diaphragm
    • Tendon reflexes are absent or profoundly decreased in neuropathies and decreased in myopathies. They should be essentially normal in de-conditioning or with residual sedative effect.
    • Plantars are unhelpful as they are equivocal
    • Lack of focal neurology or relative sparing of distal motor power (watershed infarction) tends to exclude central causes (eg CVA) or mononeuropathies.]
    • Distribution of weakness is symmetrical in all other causes and tends to be more profound proximally in myopathies, facial involvement tends to occur more in myopathies than in neuropathies (rare exception Miller-Fisher GBS variant).
    • Muscle wasting may be present with myopathies and when there exists a pre-existing myopathy or neuropathy. Muscle fasciculation is uncommon but if present supports a lower motor neuron lesion, severe neuropathy or myopathy.

Investigations:

    • Check biochem and ABGs (U&E’s, LFT’s – espy K, PO4, Ca, Mg, pH, PaCO2), FBE and inflammatory markers, Vit D and Gentamicin level
    • Review cultures and sensitivities and abx used to determine the possibility of ongoing or resistant infection.
    • CK – timing of test to be considered (Best done in first 7 days of illness – if not performed add test to previous blood samples - Elevated in myopathies
    • Nerve conduction studies and Electromyographic studies help support diagnoses of neuropathy and myopathy (vs severe deconditioning or central causes)
    • CSF analysis (GBS), may be required .
    • Muscle Biopsy may be required.
    • MRI if central cause suspected or NCS and EMG don’t support CINM

Discussion

The college answer is extensive and covers the territory well.

For revision purposes, several chapters exist locally:

From the above resources (specifically, from the table in chapter 5.5.1) I will pick some relevant conditions and put them in a sensible pattern to assist their recollection:

Differential diagnosis for weakness:

  • Central:
    • Spinal or brainstem ischaemia (unlikely)
  • Peripheral nerve:
    • Autoimmune polyneuropathy, eg. Guillain-Barre syndrome
    • Criticial illness neuromyopathy
    • Nutritional polyneuropathy, eg. B12 deficiency
  • Neuromuscular junction
    • Myasthenia gravis (unlikely)
    • Aminoglycoside-induced weakness (in association with neuromuscular junction blockers)
  • Muscle
    • Atophy due to prolonged ICU stay, hypercatabolic state and malnutrition
    • Criticial illness neuromyopathy
    • Steroid myopathy
    • Electrolyte derangement, eg. hypophosphataemia, hypocalcemia, hypermagnesemia or hypokalemia

Clinical examination

  • GCS (brainstem-damaged or "locked in" syndrome)
  • Gross bilateral power (looking for symmetry, distal sparing, lateralising motor feature)
  • Cranial nerve examination (Normal cranial nerves suggest a purely peripheral problem)
  • Tendon reflexes (absent in neuropathies, decreased in myopathies)
  • Fatiguability (Myasthenia gravis vs. "reverse" fatiguability with Lambert-Eaton syndrome)

A panel of investigations:

  • Electrolyte levels
  • CK level
  • B12 level
  • Inflammatory markers
  • Lumbar puncture
  • Nerve conduction studies
  • Electromyography
  • MRI of the brainstem and spine
  • Muscle biopsy if no satisfactory explanation is found.

References

References

Oh's Intensive Care manual:

Chapter   51   (pp. 568)  Acute  cerebrovascular  complications by Bernard  Riley  and  Thearina  de  Beer

Chapter   57   (pp. 617)  Neuromuscular  diseases  in  intensive  care by George  Skowronski  and  Manoj  K  Saxena

Yuki, Nobuhiro, and Hans-Peter Hartung. "Guillain–Barré syndrome." New England Journal of Medicine 366.24 (2012): 2294-2304.

Jani, Charu. "Critical Illness Neuropathy." Medicine (2011): 237.

Young, G. Bryan, and Robert R. Hammond. "A stronger approach to weakness in the intensive care unit." Critical care 8.6 (2004): 416.