What is the approach to diagnosing and managing a patient presenting with symptoms of EDS (Ehlers-Danlos Syndrome or Excessive Daytime Sleepiness)?

Approach to Diagnosing and Managing Ehlers-Danlos Syndrome (EDS) and Excessive Daytime Sleepiness (EDS)

For patients presenting with symptoms suggestive of Ehlers-Danlos Syndrome or Excessive Daytime Sleepiness, a structured diagnostic approach focusing on specific clinical features is essential, followed by targeted treatment based on the confirmed diagnosis.

Differentiating Between the Two Conditions

Ehlers-Danlos Syndrome (EDS)

• Hypermobile EDS is characterized by joint hypermobility, skin findings (hyperextensibility, smooth velvety skin), and joint pain or recurrent dislocations 1
• Diagnosed using the 2017 International Classification criteria which includes assessment of joint hypermobility and exclusion of other connective tissue disorders 1
• May present with sleep disturbances due to pain from frequent dislocations during sleep 2
• Associated with higher prevalence of obstructive sleep apnea (32% vs 6% in matched controls) which contributes to excessive daytime sleepiness 3

Excessive Daytime Sleepiness

• Defined as inability to maintain wakefulness during major waking episodes of the day 4
• Assessed using validated tools such as the Epworth Sleepiness Scale (ESS) 5
• Common causes include:
  • Primary sleep disorders (OSA, narcolepsy, idiopathic hypersomnia) 4
  • Medical conditions (neurological disorders, endocrine disorders) 4
  • Medication effects (benzodiazepines, opioids, antihistamines) 4
  • Poor sleep hygiene and insufficient sleep 4

Diagnostic Approach

For Suspected Ehlers-Danlos Syndrome

1. Assess for joint hypermobility and skin hyperextensibility 1
2. Document history of joint dislocations or subluxations 1
3. Evaluate for associated symptoms:
   • Chronic pain 1
   • Fatigue 1
   • Orthostatic intolerance 1
   • Gastrointestinal disorders 1
4. Screen for sleep disorders, particularly OSA, given the high prevalence in EDS patients 3

For Suspected Excessive Daytime Sleepiness

1. Obtain detailed sleep history:
   • Sleep duration and quality 5
   • Presence of snoring, witnessed apneas, or gasping 5
   • Episodes of cataplexy (sudden muscle weakness triggered by emotions) 5
   • Hypnagogic hallucinations or sleep paralysis 5
2. Use validated screening tools:
   • Epworth Sleepiness Scale (ESS) to quantify sleepiness 5
   • STOP questionnaire for OSA risk 4
3. Conduct appropriate sleep studies:
   • Polysomnography (PSG) for suspected OSA or other sleep disorders 5
   • Multiple Sleep Latency Test (MSLT) for suspected narcolepsy or idiopathic hypersomnia 5
4. Laboratory testing:
   • Thyroid function tests 5
   • Complete blood count 5
   • Liver function tests 5
   • Ferritin levels if restless legs syndrome is suspected 4

Management Approach

For Ehlers-Danlos Syndrome

1. Symptom management:
   • Physical and occupational therapy to strengthen muscles and improve joint stability 1
   • Pain management strategies 1
2. Prevention of joint injury:
   • Education about activities to avoid 1
   • Appropriate bracing or supports 1
3. Management of associated sleep disorders:
   • Screening and treatment for OSA if present 3
   • Addressing pain-related sleep disruption 2

For Excessive Daytime Sleepiness

If due to Obstructive Sleep Apnea:

1. Continuous Positive Airway Pressure (CPAP) therapy 5
2. Consider modafinil for residual sleepiness despite CPAP:
   • Starting dose 200 mg daily 6
   • Has shown significant improvement in wakefulness as measured by Maintenance of Wakefulness Test and Clinical Global Impression of Change 6

If due to Narcolepsy:

1. Pharmacologic treatment:
   • Modafinil is recommended as first-line treatment for excessive daytime sleepiness 5, 6
   • Starting dose for elderly patients: 100 mg once upon awakening, can be increased to 200-400 mg daily 5
   • Alternative stimulants: methylphenidate, amphetamines 5
   • For cataplexy: sodium oxybate or antidepressants 5
2. Behavioral interventions:
   • Scheduled short naps (15-20 minutes) around noon and late afternoon 5
   • Regular sleep-wake schedule 5
   • Avoidance of alcohol and heavy meals 5

If due to Idiopathic Hypersomnia:

1. Similar pharmacologic approach as narcolepsy:
   • Modafinil (100-400 mg daily) 5
   • Traditional stimulants if modafinil is ineffective 5

Special Considerations and Pitfalls

• Patients with EDS often have multiple comorbidities requiring coordinated care 1
• Medication side effects may be more pronounced in older adults, requiring careful dosing and monitoring 7
• Multiple causes of sleepiness often coexist, particularly in older adults with comorbidities and polypharmacy 4
• Assuming daytime sleepiness in older adults is normal aging is a common pitfall - it warrants investigation 4
• Referral to a sleep specialist is indicated when:
  • Narcolepsy or idiopathic hypersomnia is suspected 7
  • Cause of sleepiness remains unknown despite initial evaluation 7
  • Patient is unresponsive to initial therapy 7

Follow-up and Monitoring

• Regular reassessment of symptoms and treatment efficacy 5
• Monitoring for medication side effects 5
• For EDS patients with OSA, regular follow-up to ensure CPAP compliance and efficacy 5
• Occupational counseling for patients with persistent excessive sleepiness to avoid high-risk activities 5