What are the diagnostic criteria and management strategies for cerebral amyloid angiopathy (CAA)?

Diagnostic Criteria and Management of Cerebral Amyloid Angiopathy (CAA)

Brain MRI with gradient-echo or susceptibility-weighted imaging sequences is the gold standard for diagnosing cerebral amyloid angiopathy in living patients, with multiple lobar microhemorrhages being the hallmark finding. 1

Diagnostic Criteria for CAA

Modified Boston Criteria for CAA Diagnosis:

1. Definite CAA:

   • Full postmortem examination showing:
   • Lobar, cortical, or corticosubcortical hemorrhage
   • Severe CAA with vasculopathy
   • Absence of other diagnostic lesion

2. Probable CAA with supporting pathology:

   • Clinical data and pathologic tissue (evacuated hematoma or cortical biopsy) showing:
   • Lobar, cortical, or corticosubcortical hemorrhage
   • Some degree of CAA in specimen
   • Absence of other diagnostic lesion

3. Probable CAA:

   • Clinical data and MRI or CT showing:
   • Multiple hemorrhages restricted to lobar, cortical, or corticosubcortical regions
   • Age ≥55 years
   • Absence of other cause of hemorrhage

4. Possible CAA:

   • Clinical data and MRI or CT showing:
   • Single lobar, cortical, or corticosubcortical hemorrhage
   • Age ≥55 years
   • Absence of other cause of hemorrhage

Key Diagnostic Features on Imaging

• MRI findings: 1, 2

  • Multiple lobar microhemorrhages (primary finding)
  • Cortical superficial siderosis
  • White matter hyperintensities
  • Cerebral edema (particularly in inflammatory CAA)
  • Lobar macrohemorrhages

• Amyloid PET limitations: 1

  • Cannot distinguish between parenchymal amyloid plaques and vascular amyloid
  • High age-associated prevalence of amyloid positivity (>50% in persons aged 80-90)
  • Positive in both CAA and Alzheimer's disease

Histopathological Diagnosis

• Tissue examination: 1
  • Congo red or thioflavin staining showing apple-green birefringence under polarized microscopy
  • Amyloid-β immunohistochemistry
  • Assessment of:
    • Focal vs. widespread involvement
    • Meningeal vs. cortical involvement
    • Arteriolar vs. capillary involvement
    • Vonsattel grading of arterial wall involvement

Management Strategies

Acute Management of CAA-Related Hemorrhage

1. Immediate measures:

   • Non-contrast CT scan for diagnosis 3
   • Assess neurological status using standardized severity score
   • Determine time of symptom onset

2. Coagulopathy management: 3

   • Immediate reversal of anticoagulation if present
   • Maintain platelet count above 50×10^9/L

3. Monitoring and complications: 3

   • Monitor for increased intracranial pressure
   • Consider ICP monitoring in patients with GCS ≤8
   • Head elevation to 30 degrees
   • Monitor for clinical and electrographic seizures

Long-term Management

1. Blood pressure control: 4

   • Strict treatment of arterial hypertension can lower the risk of intracerebral hemorrhage by 77% in persons with probable CAA

2. Medication considerations: 4

   • Exercise caution with oral anticoagulants and antiplatelet agents
   • Avoid statins after lobar ICH (increases recurrent hemorrhage risk from 14% to 22%)
   • ApoE ε2 and ε4 alleles associated with increased hemorrhage risk

3. Monitoring disease progression: 5

   • Gradient-echo MRI can track progression (50% of patients develop new petechial hemorrhages over 1.5 years)

4. Special considerations for amyloid-modifying therapies: 1

   • Patients with >4 microhemorrhages should be excluded from amyloid-modifying therapies
   • Monitor for amyloid-related imaging abnormalities (ARIA)

Clinical Presentations of CAA

• Spontaneous lobar intracerebral hemorrhage
• Transient focal neurologic episodes ("amyloid spells")
• Progressive cognitive decline leading to dementia
• Inflammatory CAA subtype with rapid cognitive decline and neurological deficits 2, 6

Pitfalls and Caveats

1. Diagnostic challenges:

   • CAA can be misdiagnosed as seizures or transient ischemic attacks in the emergency department 2
   • Amyloid PET cannot distinguish between amyloid angiopathy and parenchymal plaques 1

2. Treatment risks:

   • 70% of patients who sustained hemorrhage after thrombolytic therapy were found to have CAA 4
   • Higher risk of treatment-associated brain hemorrhage in patients with microhemorrhages receiving systemic lytic treatment 4

3. Prognosis:

   • Currently no disease-modifying treatments available 6, 7
   • Inflammatory CAA subtype should be recognized early and treated promptly for better outcomes 6

4. Age considerations:

   • Prevalence increases with age (30% in 7th decade, 50% in 8th-9th decades) 4
   • Sporadic CAA almost exclusively occurs in patients over 55 years old