Inflammatory CAA protocol

Diagnosis and Treatment of cerebral amyloid angiopathy–related inflammation (CAA-RI)

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Diagnosis

Definite CAA-RI : Tissue-based evidence of CAA-related inflammation in the cerebral vasculature.

• CAA identified by Congo Red or immunostaining of pathological samples
• Evidence of perivascular or vascular inflammatory infiltrate associated with CAA-affected blood vessels
• No other causative lesion identified.

Probable CAA-RI : Clinical and neuroimaging evidence strongly suggestive of CAA-related inflammation.

• Pattern of hemorrhagic lesions consistent with probable CAA (multiple exclusively lobar-based hemorrhages or microbleeds, no other definite cause of intracerebral bleeding such as vasculitis, tumor, vascular malformation, or coagulopathy)
• MRI T2/FLAIR-sequence changes of confluent subcortical white matter hyperintensities and/or cortical sulcal hyperintensities
• These above described changes are often focal or asymmetric, typically with little or no contrast enhancement
• CSF abnormalities of mildly elevated protein and presence of leukocytes may be seen, but normal CSF does not rule out the diagnosis.

Treatment

• The strongest basis for treatment is the finding of Definite CAA-RI by brain/leptomeningeal biopsy. Empiric treatment can also be considered for Probable CAA-RI when the neuroimaging features appear clear-cut.
• Five-day course of high-dose corticosteroids (e.g. IV methylprednisolone 500mg-1g / day x 5 days) as an inpatient or outpatient followed by outpatient treatment with a tapering oral corticosteroid dose (e.g. PO prednisone 40-60 mg/day, reduced in weekly increments to a target of approximately 10 mg/day).
• During the course of steroid treatment, the treating clinician may also wish to consider the following if appropriate and depending on the length of treatment:
  • Ensure adequate calcium (1200-1500mg/day), and vitamin D (400-800 units/day).(Two-three caltrate tabs daily)
  • Yearly bone density measurements
  • Vitamin D level every 6 months. Supplement if below 30ng/ml
• Re-imaging and clinical follow-up approximately 3-4 weeks after initial treatment to monitor radiographic changes and clinical status. If there is radiographic resolution of the subcortical/sulcal hyperintense lesions, it is reasonable to consider continuing the downward steroid taper with the goal of discontinuing.
• Radiographic resolution may precede or occur in the absence of clinical change. In these cases, other reasons for clinical impairment (progression of underlying Alzheimer’s or CAA pathology) should be sought.
• Consider repeat lumber puncture on follow-up, especially in cases with baseline CSF abnormalities and ambiguous neuroimaging and clinical response to treatment.
• If there the is no or poor radiographic and clinical improvement after approximately 8 to 10 weeks of steroid treatment, consider changing the immunosuppressive regimen to cyclophosphamide, 1-2 mg/kg/day PO for 2 weeks. In this situation, it is also reasonable to consider confirming Definite CAA-RI by brain biopsy prior to initiating cyclophosphamide.
• Other immunosuppressive agents may be further alternatives in highly refractory cases, although clinical experience with these agents remains very limited

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Last updated: 1/1/1

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