What is the treatment for headache in Acute Reversible Ischemic Neurological Deficit (ARIA) and Posterior Reversible Encephalopathy Syndrome (PRES)?

Treatment for Headache in ARIA and PRES

The treatment of headache in ARIA (Amyloid-Related Imaging Abnormalities) and PRES (Posterior Reversible Encephalopathy Syndrome) should primarily focus on addressing the underlying cause while providing symptomatic relief with non-steroidal anti-inflammatory drugs (NSAIDs) or paracetamol, avoiding opioids. 1

Understanding ARIA and PRES

ARIA

ARIA occurs in the context of anti-amyloid therapies for Alzheimer's disease and presents in two forms:

• ARIA-E: Vasogenic edema or sulcal effusions
• ARIA-H: Hemosiderin deposits (microhemorrhages or superficial siderosis)

Most cases of ARIA are asymptomatic, but when symptoms occur, headache is among the most common, along with confusion and visual disturbances 1.

PRES

PRES is characterized by reversible vasogenic edema primarily affecting the posterior cerebral regions, often associated with hypertension, immunosuppressive therapy, or eclampsia.

Treatment Algorithm for Headache in ARIA and PRES

Step 1: Address the Underlying Cause

• For ARIA: Temporarily suspend the amyloid-modifying therapy until symptoms resolve 1, 2
• For PRES: Control blood pressure, remove offending agents, treat seizures if present

Step 2: Symptomatic Headache Management

First-line options:

• NSAIDs (particularly indomethacin may be beneficial due to its ICP-reducing effects) 1
• Paracetamol (acetaminophen) 1
• Consider gastric protection when using NSAIDs, especially for prolonged use 1

Important cautions:

• Avoid opioids as they are not recommended for headache management 1
• Avoid medications that could worsen the condition (vasoconstrictors in PRES)

Step 3: For Severe or Persistent Symptoms

For ARIA with severe symptoms:

• In severe symptomatic cases of ARIA-E, IV steroids may be considered (based on case reports) 1
• Monitor with follow-up MRI to assess resolution 2

For persistent headaches with migrainous features:

• Consider migraine-specific treatments based on headache phenotype 1
• Triptan acute therapy may be used in combination with NSAIDs or paracetamol and an antiemetic with prokinetic properties 1
• Limit triptans to 2 days per week or maximum 10 days per month 1

Special Considerations

Monitoring

• Regular MRI monitoring is essential in ARIA to track resolution 2
• For ARIA, most cases resolve spontaneously within 4-12 weeks

Risk Factors for ARIA

• ApoE ε4 carrier status is a significant risk factor for ARIA-E 1, 3
• Higher doses of amyloid-modifying therapies increase risk 1
• Prior microhemorrhages increase risk for ARIA-H 3

Medication Overuse Risk

• Be vigilant about medication overuse headache (MOH)
• Limit simple analgesics to <15 days/month and triptans to <10 days/month 1
• If medication overuse occurs, non-opioids and triptans can be stopped abruptly or weaned down within a month 1

Pitfalls to Avoid

1. Don't use opioids for headache management in these conditions 1
2. Don't delay addressing the underlying cause while treating symptoms
3. Don't overlook the possibility of medication overuse headache developing during treatment
4. Don't continue amyloid-modifying therapy without careful monitoring if ARIA is detected
5. Don't miss comorbid primary headache disorders that may require specific treatment

Lifestyle Modifications

In addition to pharmacological management, recommend:

• Adequate hydration
• Regular meals
• Sleep hygiene
• Stress management techniques 1

By following this structured approach, headaches in ARIA and PRES can be effectively managed while addressing the underlying pathophysiology and avoiding complications.