Cerebral amyloid angiopathy
Description, Causes and Risk Factors:
Cerebral amyloid angiopathy is a neoplastic, vascular well deposition of amyloid that usually presents as a focal cortical hemorrhage in the brain, but occasionally presents as a localized mass in the brain without evidence of hemorrhage. Localized amyloid (amyloid beta (A?)) deposition occurring within the media and intima of the arteries and arterioles of the brain and meninges is known as cerebral amyloid angiopathy.
There are about 30 proteins or their proteolytic products that can accumulate as amyloid in humans, and many different disease processes that can lead to amyloid formation. Because of the specific tissue affinity of amyloid deposition, which leads to accumulation in specific organs or at specific sites, only a minority of human amyloid proteins are implicated in diseases of the central nervous system. The reasons for tissue selectivity are not known and may reflect exacerbated local synthesis, protein-protein interactions with specific tissue factors, resistance to enzymatic degradation, differential blood-brain barrier permeability, dysregulated brain clearance mechanisms, or a combination of these factors.
Cerebral amyloid angiopathy seems to have slight predilection for the temporal, parietal, and occipital lobes. It is principally affects the elderly and tends to increase in prevalence with advancing age. There is no significant sex predilection.
CAA has a prevalence of 90% to 96% in patients with Alzheimer disease (AD) and is present in 30% of non-demented individuals over the age of 60 years. Cerebral amyloid angiopathy reflects an age-related failure of elimination of A? from the brain along perivascular lymphatic drainage pathways by which interstitial fluid (ISF) and solutes drain from the brain. This failure may be a key factor in the aetiology of AD.
The first detailed descriptions of cerebral amyloid angiopathy are attributed to Scholz, who described the deposition of proteinaceous material within cerebral artery and capillary walls and as excrescences or Drusen on the outer aspects of vessels in the brain. In the 1980s, it was from leptomeningeal arteries with CAA that Glenner and colleagues first isolated and characterized A?. The distribution of CAA in the different regions of the brain corresponds to the distribution of plaques of A?. In AD, plaques and CAA both appear to follow a sequence involving the cerebral isocortex (neocortex) at the earliest stages, then the allocortex of the hippocampus and related structures, followed by involvement of the basal ganglia and thalamus. The structures of the walls of arteries in the neocortex and basal ganglia differ and this may partly account for the less frequent deposition of A? as plaques and cerebral amyloid angiopathy in the basal ganglia. The shorter and more soluble A?40 is most abundant in CAA, whereas the longer and less soluble A?42 predominates in A? plaques within brain parenchyma. Apolipoprotein E (ApoE) colocalizes with A?, both in plaques in the brain and with A? in the walls of capillaries and arteries in CAA. Together with age, APOE ?4 genotype is a major risk factor for both CAA and AD.
Amyloid deposition in cerebral blood vessels can haveseveral clinical consequences. First, it can remain asymptomatic, as suggested by the neuropathological observation that during “normal” ageing approximately 50% ofindividuals over 80 years of age have cerebral amyloid angiopathy. Second, it canweaken the vessel wall, causing rupture and intracerebralhemorrhage (ICH). Finally, it can obliterate the vessellumen, leading to ischemia (cerebral infarction, “incomplete infarction,” and leukoencephalopathy). Focal neurological deficits, disturbances of consciousness, step-wisedementia, and death can occur as a consequence of thesevascular mechanisms.
Common symptoms may include:
- Headache (usually in a specific part of the head).
- Neurologic changes that may start suddenly, including: confusion, double vision, decreased vision, sensation change, speech difficulties.
- Stupor or coma.
The differential diagnosis may include primary brain tumors like gliomas, atypical vascular infarction, cardioembolic stroke, cerebral aneurysms, frontal and temporal lobe dementia, frontal lobe syndromes, intracranial hemorrhage, partial epilepsies, and posttraumatic epilepsy
The diagnosis of cerebral amyloid angiopathycan only be made with certaintyafter histologic investigation of affected brain tissue,obtained at autopsy or brain-biopsy. In practice it is veryoften found unexpectedly at postmortem investigation.Noninvasive diagnostic criteria have been developed toreliably diagnose CAA during life. This classificationhas been validated against pathological data. CAA is considered “probable with supporting pathology” when, incombination with appropriate clinical data, pathologic tissue from a biopsy performed at the time of hematomaevacuation reveals amyloid angiopathy. Cerebral amyloid angiopathy is considered “probable” if there is an appropriate clinical historyas well as imaging findings of multiple cortical-subcortical hematomas in a patient 55 years or older, with noother clinical or radiologic cause of hemorrhage. Finally,clinical data suggesting CAA and the imaging finding ofa single cortical-subcortical hematoma in a patient olderthan 55 years, without other causes of hemorrhage, leadsto a diagnosis of “possible” CAA. Hereditary CAA canbe suspected based on the presence of a family history ofcerebral hemorrhages and the young age of the patient.
A physical exam can be relatively normal if you have a small bleed, but you may show some brain function changes. It is important for the doctor to ask detailed questions about your medical history. Your symptoms and the results of your physical exam and any imaging tests may cause your doctor to suspect this problem.
- A CT scan or MRI of the head may show:bleeding in the brain, signs of prior bleeding in the brain
- Magnetic resonance angiography (MRA) of the brain can help with the diagnosis of large bleeds and may be used to rule out arteriovenous malformation or aneurysm as the cause of the bleed.
- Another type of MRI scan can help show tiny areas where blood has escaped from blood vessels into brain tissue.
Elimination of A? from the brain involves enzymic degradation, its absorption into the blood and drainage of A? along perivascular lymphatic drainage pathways. All of these mechanisms appear to fail as the brain and cerebral arteries age. One of the major consequences of this failure is the obstruction of lymphatic drainage of fluid and solutes from the brain by CAA that results in the accumulation of insoluble and soluble A?s in the brain and probably other metabolites that would lead to loss of homeostasis of the neuronal environment. Accumulation of hyperphosphorylated tau in neurons and failure of neuronal function may ensue from the loss of homeostasis.
The therapeutic challenge is to ensure adequate elimination of A? from the ageing brain and along ageing cerebral arteries. Pharmacological intervention to enhance enzymic degradation of A? and absorption of A? into the blood is one obvious direction to take. Resolving the inadequacies of the ageing lymphatic drainage pathway will entail a greater understanding of its physiology and how the various elements such as basement membranes, smooth muscle cells and perivascular cells interact and how they change with age. Establishing the role played by ApoE in the elimination of A? and harnessing this information for the design of therapies may help to prevent the accumulation of amyloid in blood vessel walls and brain in AD.
The management of cerebral amyloid angiopathy-related intracranial hemorrhage (ICH) is identical to the standard management of ICH. Pay special attention to reversing anticoagulation, managing intracranial pressure, and preventing complications. If coexisting vasculitis is found on angiography and brain biopsy, long-term treatment (up to 1 y) with steroids and cyclophosphamide is indicated.
A syndrome of subacute cognitive decline, seizures, and white matter changes on MRI with perivascular inflammatory changes on biopsy was recently described. Some patients improved clinically (but not to baseline) when given corticosteroids or cyclophosphamide.
Surgical treatments are controversial. A deteriorating neurological status, intractable intracranial hypertension, and the size of the hemorrhage are major factors. Patients with a hemorrhagic volume between 20 and 60 cc who exhibit a progressive decline in consciousness may be good candidates for surgical evacuation of the hematoma. Otherwise, conservative treatment and medical management are keys in treating hemorrhage related to cerebral amyloid angiopathy. Neuropsychological testing helps assess for the presence of cognitive impairment.
NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.
DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.