Do Guillain-Barré Syndrome (GBS) and Duchenne muscular dystrophy (DMD) cause decreased hypocretin levels in cerebrospinal fluid (CSF)?

Hypocretin Levels in Guillain-Barré Syndrome and Duchenne Muscular Dystrophy

Guillain-Barré Syndrome (GBS) can cause decreased hypocretin levels in cerebrospinal fluid, while there is no evidence that Duchenne muscular dystrophy affects CSF hypocretin levels. 1, 2, 3

Guillain-Barré Syndrome and Hypocretin

Evidence of Decreased Hypocretin in GBS

• Multiple studies have demonstrated that GBS can be associated with reduced CSF hypocretin-1 (orexin-A) levels:
  • In a 2003 study, 7 out of 28 GBS patients had undetectably low hypocretin-1 levels (<100 pg/mL), and an additional 11 GBS patients had moderately reduced levels 1
  • Low hypocretin levels in GBS typically occur early in the disease course and are associated with upper CNS level abnormalities 1
  • Another study confirmed that some GBS patients have lower levels of CSF hypocretin-1 3

Clinical Significance

• Hypocretin reduction in GBS is notable because undetectable CSF hypocretin-1 levels are otherwise highly specific to narcolepsy, making GBS one of the rare exceptions 2
• The mechanism behind hypocretin reduction in GBS is not fully understood but may reflect:
  • Transient dysfunction of the hypothalamus
  • Disruption of the blood-brain barrier
  • Potential autoimmune mechanisms affecting hypocretin-producing neurons 4, 2

CSF Findings in GBS

While hypocretin changes are not part of the standard diagnostic criteria for GBS, other CSF findings are well-established:

• The classic CSF finding in GBS is albumino-cytological dissociation (elevated protein with normal cell count) 5, 6
• However, protein levels are normal in 30-50% of patients in the first week after disease onset and 10-30% in the second week 5
• CSF examination is primarily used to rule out other causes of weakness rather than confirm GBS diagnosis 5
• Age-dependent interpretation of CSF protein is important, as using the conventional upper reference limit (0.45 g/L) without age adjustment may lead to false-positive results 7

Duchenne Muscular Dystrophy and Hypocretin

• There is no evidence in the provided literature suggesting that Duchenne muscular dystrophy affects CSF hypocretin levels
• DMD is a genetic disorder affecting dystrophin protein expression, primarily impacting skeletal and cardiac muscle rather than the central nervous system structures that produce hypocretin

Clinical Implications

• Decreased hypocretin levels in GBS patients may contribute to some neurological manifestations but are not used for diagnostic purposes
• Standard GBS diagnosis relies on clinical features, CSF protein levels, and electrodiagnostic studies 5, 6
• For patients with GBS who exhibit unusual sleep disturbances or altered consciousness, checking hypocretin levels might provide additional insights, though this is not part of routine clinical practice

Pitfalls and Caveats

• Low hypocretin levels are not specific to GBS and can be seen in other neurological conditions including head trauma, CNS infections, and certain tumors 2
• CSF hypocretin measurement is not included in standard GBS diagnostic protocols 5, 6
• When interpreting CSF findings in suspected GBS, clinicians should focus primarily on protein levels and cell counts rather than hypocretin 5