Approach to the ICU patient with generalised weakness

The college love generalised weakness. It is frequently lurking in the background of hot cases and it has appeared in many previous SAQs:

Additionally, weakness (specifically myasthenia gravis) became the topic of Viva 1 from the second paper of 2015. Copious words are written about this issue in many reputable sources. The objective of this page is not to reproduce the same information you can find in UpToDate or in Oh's Manual. The point is to have a quick reference summary of relevant differences, and a framework for answering CICM SAQs on this topic.

This ties in with several other local summaries:

The canonic resource is Oh's Chapter   57  (pp. 617)-   Neuromuscular  diseases  in  intensive  care by George  Skowronski  and  Manoj  K  Saxena. However, if one were to limit one's reading to one resource, one should make it the 2006 article by Upinder Dhand from Respiratory Care, titled "Clinical approach to the weak patient in the intensive care unit."

Differential diagnosis of weakness in the critically ill patient

In order to render easier the process of discussing these conditions, I have arranged them in a table, together with their specific features and diagnostic methods. This table was in turn inspired by Table 3 ("Semiology of main peripheral nervous system syndromes") from a 2014 issue of the ESICM "Pragmatic Guidelines" for the neurological examination of critically ill patients.

Causes of Weakness in Intensive Care Patients
Level of pathology Aetiology Unique features Diagnostic approach
Brainstem Locked-in syndrome

Sudden onset

Vertical gaze and eyelid opening should be preserved



Motor neuron Motor neuron disease (eg, amyotrophic lateral sclerosis)

Increased reflexes

Assymmetry of signs

Increased tone

Upper motor neuron signs

Characteristic fasciculations

EMG - there will be "jitter"

Diagnosis of exclusion

Spinal cord Transverse myelitis

Motor and sensory loss below the affected level


Compression by tumour

Gradual onset, may be lateralising


LP (for cytology)

Compression by abscess

Subacute onset, may be lateralising



Spinal cord infarction

Focal neurology

Sudden onset


Peripheral nerve Critical Illness Neuromyopathy

Normal cranial nerves

Symmetrical features;

Reflexes absent

Diaphragm involved

CK slightly elevated

Clinical diagnosis

Guillain–Barré syndrome

Ascending patterns

History of recent febrile illness or immunization

Reflexes absent

No upper motor neuron signs

LP (increased CSF protein)

Nerve conduction studies (conduction will be delayed)

Vitamin B12 deficiency

Glove and stocking distribution of sensory loss

Serum B12 levels

Heavy metal poisoning    
Neuromuscular junction Myasthenia gravis

First comes diplopia;

eyes and cranial nerves are hit first

There is characteristic fatiguability: weakness increases with sustained exercise.

Fade and post tetanic facilitation is present on nerve stimulator testing

It will respond to anticholinesterases.

Acetylcholine receptor antibodies


Edrophonium challenge

Lambert–Eaton syndrome

Associated malignancy

proximal muscle weakness

diplopia is uncommon

Opposite of fatiguability: weakness resolves with sustained exercise



Starts with the cranial nerves

Botulinum toxin detection

Organopshosphate poisoning

Cholinergic syndrome

Mixed cholinesterase studies

Muscle Steroid myopathy

Proximal weakness

Symmetrical features;

Reflexes reduced

Clinical diagnosis

Resolves with withdrawal of steroids

Electrolyte disturbance

Generalised weakness

Electrolyte levels

Atophy due to hypercatabolic state and malnutrition

Normal reflexes

Markers of malnutrition

Critical Illness Neuromyopathy

Normal cranial nerves

Symmetrical features;

Reflexes absent

Diaphragm involved

CK slightly elevated

Clinical diagnosis

Clinical examination:

Level of consciousness

  • Perform a GCS. The brainstem-damaged or "locked in" patient will not perform well in this test.
  • The patient with critical illness polyneuromyopathy (CIP) will be conscious.

Gross bilateral power

  • Symmetry favours CIP
  • Sparing of distal motor power tends to exclude focal CNS lesions
  • Assymetry of motor findings favours a focal CNS lesion.
    • A "level" of motor features suggests some spinal pathology
    • Lateralising motor features suggest motor cortex pathology
  • Fatiguability (Myasthenia gravis vs. "reverse" fatiguability with Lambert-Eaton syndrome)

Cranial nerve examination

  • Normal cranial nerves suggest a purely peripheral or spinal problem.

Tendon reflexes

  • Tendon reflexes are absent in neuropathies, and merely decreased in myopathies. They should be essentially normal in de-conditioning or with residual sedative effect.


A panel of standard investigations which will exclude many of the above would include the following tests and imaging studies:

  • Electrolyte levels
  • CK level
  • B12 level
  • Acetylcholine receptor antibodies (for myasthenia gravis)
  • CXR looking for malignancy (as support for a diagnosis of Eaton-Lambert syndrome)
  • Inflammatory markers
  • Lumbar puncture
  • Nerve conduction studies
  • Electromyography
  • MRI of the brainstem and spine
  • Muscle biopsy if no satisfactory explanation is found.


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.

Mareska, Michael, and Laurie Gutmann. "Lambert-Eaton myasthenic syndrome." Seminars in neurology. Vol. 24. No. 2. [New York]: Thieme-Stratton Inc.,[c1981-, 2004.

Reeves and Swenson have an excellent online textbook chapter (12) entitled "Evaluation of the Patient with Weakness"

Centers for Disease Control and Prevention (CDC). "Tetanus surveillance---United States, 2001-2008." MMWR. Morbidity and mortality weekly report 60.12 (2011): 365.

Schiavo, Giampietro G., et al. "Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin.Nature359.6398 (1992): 832-835.

O'Malley, Cynthia D., et al. "Tetanus associated with body piercing." Clinical infectious diseases 27.5 (1998): 1343-1344.

Cook, T. M., R. T. Protheroe, and J. M. Handel. "Tetanus: a review of the literature." British Journal of Anaesthesia 87.3 (2001): 477-487.

Lockman, Juliana, and Ted M. Burns. "Stiff-person syndrome." Practical neurology 7.2 (2007): 106-108.

McLeod, Bruce C. "Therapeutic apheresis: use of human serum albumin, fresh frozen plasma and cryosupernatant plasma in therapeutic plasma exchange."Best Practice & Research Clinical Haematology 19.1 (2006): 157-167.

Raphael, J. C., et al. "Plasma exchange for Guillain-Barré syndrome." Cochrane Database Syst Rev 2.2 (2002).

Reimann, P. M., and P. D. Mason. "Plasmapheresis: technique and complications." Intensive care medicine 16.1 (1990): 3-10.

Coutinho, Agnes E., and Karen E. Chapman. "The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights." Molecular and cellular endocrinology 335.1 (2011): 2-13.

Sharshar, Tarek, et al. "Neurological examination of critically ill patients: a pragmatic approach. Report of an ESICM expert panel." Intensive care medicine 40.4 (2014): 484-495.

Dhand, Upinder K. "Clinical approach to the weak patient in the intensive care unit." Respiratory care 51.9 (2006): 1024-1041.