Neuro-Ophthalmology and Cerebral Amyloid Angiopathy
The neuro-ophthalmologic manifestations of cerebral amyloid angiopathy.
Cerebral Amyloid Angiopathy (CAA) is a disorder that affects small to medium-sized blood vessels in the brain and leptomeninges because of beta-amyloid plaque buildup within the adventitia and media layers.
CAA is age dependent and uncommon in patients under 60-65 years old. Moderate and severe cases are strongly age-dependent with increased incidence in the elderly population.
The precise pathophysiology of CAA is not known but the likely process is the abnormal creation and destruction of amyloid beta protein, which is a product from amyloid precursor protein. This product then accumulates in the walls of blood vessels affecting the normal structures and leading to structural defects and increased risk of hemorrhage.
Ophthalmologic Symptoms, Signs, and Exam Findings
CAA is usually asymptomatic but when clinical symptoms arise, they are dependent on the location and size of the hemorrhage. The deposition of amyloid weakens the blood supply and can occur in various areas of the brain. Although this Eyewiki focuses on the signs for ophthalmology, other neurologic manifestations include cognitive decline, dementia, headaches, seizures, and focal neurological deficits.
Visual loss in CAA is typically due to occipital lobe or optic radiation involvement causing homonymous hemianopsia or cortical visual loss.4 Although CAA has associations with inflammatory retinal vasculitis, optic disc edema, retinal and peripapillary hemorrhages are uncommon presentations.
The retinal changes in CAA include thinning of the retinal nerve fiber layer detected with optical coherence tomography (OCT) and may be an early indication of the disease by illustration of microbleeds. The amyloid deposition in the blood vessel walls affects the blood supply to the retina. This pathology occurred in a case of sporadic CAA involving elevated intraocular pressure that resulted in vision loss due to neovascular glaucoma with ischemia to the retina.
The vision loss due to intracranial hemorrhage in CAA can affect the visual association pathways and produce visual agnosias. One case of CAA developed prosopagnosia, an inability to recognize faces, localized to the fusiform face area of the occipitotemporal region.
The most common ophthalmic presentation in CAA however is involvement of the occipital lobe, leading to homonymous hemianopsia or cortical visual loss if bilateral.
CAA is a clinical diagnosis supported by neuroimaging, but a definitive diagnosis requires a biopsy. Most cases occur antemortem without histopathologic confirmation. On pathology CAA shows positive Congo Red dye showing “apple-green” birefringence for amyloid.
Differential diagnosis for CAA
The differential diagnosis of CAA includes other causes of intracranial hemorrhage (e.g., hemorrhagic tumor, arteriovenous malformation, trauma, hemorrhagic stroke, neurocysticercosis, and hypertensive hemorrhagic microangiopathy).
Traditional CT and MR imaging have difficulty highlighting the recurrent multifocal microbleeds associated with CAA. The use of gradient-echo MRI (GRE) and susceptibility-weighted MRI (SWI) are useful tools in evaluating CAA since they show hypointense lesions in blood extravasation from microangiopathy. A specific finding towards CAA is cortical superficial siderosis.
The Boston Criteria is the diagnostic criteria to diagnose CAA. Definite CAA is post-mortem with severe CAA vasculopathy and no other causes. Probable CAA with Supporting Pathology hemorrhage showing some degree of CAA with the absence of other cause. Probable CAA with MRI/CT has multiple hemorrhages, age is greater than or equal to 55, and absence of other causes. Possible CAA with MRI/CT showing a single hemorrhage, with age range of greater than or equal to 55, and the absence of other cause.
Classification of CAA
There are four categories of CAA determined by the deposition of beta-amyloid and inflammation. The following CAA types have beta-amyloid deposited in the vessel walls: the classic CAA, Inflammatory-CAA (I-CAA), and Amyloid Beta Related Angiitis (ABRA). Inflammation is associated with I-CAA, ABRA, and primary angiitis of the central nervous system (PACNS).
Management & Treatment Options
Since intracranial hemorrhage is common in patients with CAA, physicians may consider avoiding antiplatelet and anticoagulants in the elderly with known CAA. The role of statin therapy (a typical management strategy for hyperlipidemia in stroke) is controversial and both aspirin and statin therapy may have a theoretical increased risk for recurrent hemorrhage in CAA. The precise role of these agents in CAA remains ill-defined and controversial. Managing hypertension is important as CAA related hemorrhages may be more common with uncontrolled blood pressure. There has not been an improvement in survival with surgical removal of the hemorrhage in the absence of significant mass effect.
This will vary between patients because it is dependent on the size, location, and age of the patient. Smaller, superficial, and younger ages have a more favorable prognosis.
Clinicians should be aware of the clinical presentation of CAA (typically, multifocal, recurrent intracerebral hemorrhages) and that homonymous hemianopsia or cortical visual loss can occur in optic radiation or occipital lobe CAA. Modern neuroimaging including CT and MRI including SWI and gradient echo can identify microhemorrhages which can make a clinical and radiographic diagnosis without the need for confirmatory biopsy. Traditional stroke reduction measures including anti-platelet use (e.g., aspirin) and statin therapy remain controversial in CAA.
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