Can patients with Critical Illness Myopathy (CIM) have elevated protein levels in cerebrospinal fluid (CSF)?

Elevated Protein Levels in Cerebrospinal Fluid (CSF) in Critical Illness Myopathy (CIM)

Yes, patients with Critical Illness Myopathy (CIM) can have elevated protein levels in cerebrospinal fluid (CSF), though this is not a common or characteristic finding specific to CIM diagnosis.

Pathophysiology and CSF Findings in CIM

• CIM is a neuromuscular disorder that frequently develops in critically ill patients hospitalized in intensive care units for more than one week, characterized by muscle weakness and wasting with a decreased myosin/actin ratio 1, 2.
• Unlike conditions such as Guillain-Barré syndrome (GBS) where CSF protein elevation is a characteristic finding (albumino-cytological dissociation), CIM does not typically present with specific CSF abnormalities as a diagnostic feature 3.
• When CSF protein elevation does occur in CIM patients, it may be related to:
  • Blood-brain barrier disruption that can occur during critical illness 3
  • Systemic inflammatory response syndrome (SIRS) or sepsis, which are major risk factors for CIM 1
  • Concomitant neurological complications of critical illness 4

Biomarkers in CSF During Critical Illness

• In critically ill patients, several biomarkers may be elevated in CSF, including:
  • Neurofilament light chain protein (NfL), which indicates axonal damage and has been found elevated in 63% of critically ill patients with neurological symptoms 4
  • Glial fibrillary acidic protein (GFAP), which is almost exclusively expressed in astrocytes and may be elevated in 16% of critically ill patients 3, 4
  • Total tau protein, which may be elevated in 37% of critically ill patients with neurological manifestations 4
  • Albumin index (CSF/serum albumin ratio), which when elevated indicates blood-brain barrier dysfunction 3

Differential Diagnosis Considerations

• When elevated CSF protein is found in a patient with suspected CIM, other conditions should be considered:
  • Guillain-Barré syndrome, which classically presents with albumino-cytological dissociation (elevated protein with normal cell count) 3
  • Central nervous system infections, which typically present with both elevated protein and pleocytosis 3
  • Vascular cognitive impairment, which may show elevated CSF albumin index 3
  • Mild traumatic brain injury, which can show various CSF biomarker elevations 3

Clinical Implications

• Finding elevated CSF protein in a CIM patient should prompt consideration of:
  • Concomitant central nervous system pathology 3, 4
  • Severity of critical illness, as CSF biomarkers like NfL correlate with disease severity and time in intensive care 4
  • Need for further neurological evaluation, especially if the patient has central neurological symptoms 4
  • Possible blood-brain barrier dysfunction 3

Diagnostic Approach

• When evaluating CSF in critically ill patients with suspected CIM:
  • Basic tests should include cell counts and differential, glucose and protein concentrations, Gram stain, and bacterial cultures 3
  • Consider additional specialized testing for biomarkers of CNS injury (NfL, GFAP, tau) if neurological symptoms are present 4
  • Interpret CSF findings in context with clinical presentation, as protein elevation alone is not diagnostic of any specific condition 3
  • Remember that normal CSF findings do not rule out CIM, as it is primarily a myopathy diagnosed through clinical, electrophysiological, and muscle biopsy findings 2, 5

Conclusion

While elevated CSF protein can occur in patients with CIM, particularly those with severe critical illness or concomitant neurological complications, it is not a characteristic or diagnostic feature of CIM itself. The finding should prompt consideration of other neurological conditions or complications of critical illness.