Cerebral Amyloid Angiopathy – Background, clinical presentation, investigation & diagnosis, and management

Background:
  • The underlying pathogenesis of CAA is related to amyloid beta peptide deposition in the tunica media of small and medium-sized arteries in the brain and leptomeninges
  • CAA is unrelated to systemic amyloidosis, but the amyloid peptide is similar to that in the plaques of Alzheimer’s dementia
  • Risk of CAA-related haemorrhage and earlier age at onset is associated with Apolipoprotein E (APOE) epsilon 4 allele
  • The condition is usually asymptomatic, with an estimated prevalence of 20-40% of the general population and 50-60% of patients with dementia
  • There is an increasing incidence with age, with most patients presenting after the age of 70
  • A distinct inflammatory subset of CAA, termed cerebral amyloid angiopathy-associated inflammation (CAA-I), has been identified and is due to autoimmune activity against amyloid beta peptide deposits

 

Clinical Presentation:

  • The most common manifestation of CAA is spontaneous primary lobar haemorrhage, most commonly affecting temporal and occipital lobes, and variably the cerebellum
  • The specific clinical presentation of lobar haemorrhage is related to the size and location of the haemorrhage
  • Superficial microhaemorrhages are common, and usually clinically silent, but may be associated with progressive, transient neurological symptoms
  • The risk of recurrent haemorrhage is higher in patients with CAA than in those with hypertensive intraparenchymal haemorrhage
  • In patients with CAA-I, lobar haemorrhage is less common, and patients generally present with headaches, seizures, cognitive decline and focal deficits

 

Investigation and Diagnosis:

  • Definitive diagnosis of CAA requires histopathologic examination, but should be considered in all patients over the age of 55 years with multifocal lobar haemorrhages, without another clear cause
  • The Boston Criteria for CAA allows diagnosis of probable and possible CAA based on clinical and radiological features, without the need for biopsy
  • Typical MRI findings include the presence of multiple lobar haemorrhages of varying ages, as well as microhaemorrhages and haemosiderosis on SWI series
  • MRI characteristics suggestive of CAA-I include multilobar microhaemorrhages on SWI, with confluent white matter hyperintensities on T2 sequences
  • The role of lumbar puncture and CSF examination in CAA is unclear, although elevated levels of autoantibodies against amyloid beta peptide have been reported in CAA-I
  • Genetic testing for the APOE allele is of limited value, as it is neither sensitive or specific for the diagnosis

 

Management:

  • Principles of management of CAA following a lobar haemorrhage are similar to those for hypertensive haemorrhage, with an emphasis on secondary neuroprotective strategies including intracranial pressure, blood pressure, temperature and glycaemic control
  • Due to the increased risk of recurrent haemorrhage, avoidance of aspirin and anticoagulants is advised
  • There is increasing evidence to suggest that CAA-I may be responsive to immunosuppressive therapy, with the most common treatment in the literature being corticosteroids, although treatment with cyclophosphamide, methotrexate and mycophenolate mofetil has also been reported

 

References:

  • Martucci, Sarria, Toledo et al. Cerebralamyloid angiopathy-related inflammation: imaging findings and clinical outcome. Neuroradiology 2004 56:283-289.
  • Charidimou, Gang, Werring. Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiatry 2012;83:124-137
  • Greenberg, Kasner, Wilterdink. Cerebral Amyloid Angiopathy. UpToDate. Oct 2013.
  • Image: Haacke, Del PRoposto, Chaturvedi et al. Imaging Cerebral Amyloid Angiopathy with Susceptibility-Weighted Imaging. American Journal of Neuroradiology. 2007;28:316-317

 

Source:  Internal MedicineNeurology | March 8, 2018

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