What Is Cerebral Amyloid Angiopathy?

Cerebral amyloid angiopathy is an independent cerebrovascular disease in the elderly. Its clinical features are mainly manifested in dementia, psychiatric symptoms, repeated or multiple cerebral lobe hemorrhage.

Amyloid cerebrovascular disease

Cerebral amyloid angiopathy is an independent cerebrovascular disease in the elderly. Its clinical features are mainly manifested in dementia, psychiatric symptoms, repeated or multiple cerebral lobe hemorrhage.

Chinese name

Amyloid cerebrovascular disease

From

Seniors

Nature

Cerebrovascular disease

which performed

Dementia, repetitive or multiple lobar hemorrhage

As we get older, the incidence of CAA increases dramatically. Among people aged 60 to 69 years, CAA patients account for 4.7% to 9%, but in people over 90 years old, it rises to 43% to 58%. CAA causes a higher rate of cerebral lobe hemorrhage in the elderly. A Japanese hospital study showed that between 1979 and 1990, 38% of patients who had undergone autopsy for non-traumatic cerebral lobe hemorrhage were confirmed to have CAA. In Europe and North American countries, due to the high proportion of hypertensive cerebral hemorrhage, and the improvement of the treatment of hypertension, the corresponding CAA is higher. Pathological examinations are performed on cerebral lobe hemorrhage and unexplained cerebral hemorrhage over the age of 55. 28/38) patients have CAA. There was no difference between men and women in the incidence of CAA of about 6: 5. Whether hypertension increases the risk of CAA-related cerebral hemorrhage remains unclear. CAA, cerebral lobe hemorrhage, and hypertension were not the same in patients with hypertension.

A study in a group of 107 CAA patients confirmed by pathological examination found that 32 of them had hypertension, which was only slightly higher than the incidence of hypertension in the elderly. In the study of 25 CAA patients with AD, there was no correlation between hypertension and cerebral hemorrhage. However, in the study of cerebral lobe hemorrhage, patients had a higher tendency to suffer from hypertension, between 40% and 70%. Compared with putamen, thalamus, pontine, and cerebellum, which are common sites of cerebral hemorrhage, patients with cerebral lobe hemorrhage always have a lower tendency to hypertension. Hypertension does not appear to increase the risk of recurrent cerebral lobe hemorrhage. The use of anticoagulants (such as warfarin) and thrombolytic drugs (rtPA) as a risk factor has gradually shown their clinical importance. In 32 elderly patients, cerebral lobe hemorrhage occurred while taking warfarin, and the proportion of apoE2 in patients increased, suggesting that a large number of patients were combined with CAA, 11 cases were examined by pathology, 7 of which were confirmed to have CAA. During myocardial infarction with coronary arterial thrombolysis, cerebral hemorrhage occurred in 5 cases, and autopsy confirmed severe CAA in 2 cases.

Cerebral hemorrhage occurs during anticoagulation or thrombolysis, usually in the lobe of the brain and may be more bloody. Specific molecular biological risk factors for CAA have been identified. In the hereditary record, several gene mutation positions have been found, which are related to the dominantly inherited CAA-related cerebral hemorrhage. These genetic loci are mutated in the genetic code of A and the gene of the protease inhibitor histidine C .

Patients with sporadic CAA have a genetic marker, the apoE genotype, which has been used as a marker of genetic risk factors and disease for CAA-induced cerebral lobe hemorrhage. The apoE2 allele seems to be more common among patients with CAA-related cerebral hemorrhage, and the relationship between the apoE4 allele and CAA-related cerebral hemorrhage does not seem to be related to its relationship with AD. In 91 cases of CAA-related cerebral hemorrhage, biopsy or autopsy confirmed that the frequencies of apoE2 and apoE4 alleles were 0.20 and 0.31, which were significantly higher than those of control group 0.09 and 0.14. The apoE4 allele appears to enhance the deposition of A in the formed vascular amyloid lesions. The apoE2 allele seems to be involved in the pathogenesis of amyloid deposition to vascular disease, which in turn is associated with cerebral hemorrhage.

2.1 The pathological changes of CAA itself

The lesions are mainly in the cerebral hemispheres and the occipital lobe, temporal cortex, and the small and medium arterial walls of the pia mater. Most of them are localized, patchy, and symmetrically distributed. A few can spread throughout the cerebral cortex, and the parietal and frontal lobe It can be slightly damaged, with the most prominent frontal lobe lesions. Cerebral white matter, basal ganglia, cerebellum, brain stem, and cerebral veins are rarely affected.

2.1.2 The brain volume shrinks, the cortex shrinks, and the brain weight decreases as seen by the naked eye. On average, the brain weight is reduced by 150 to 200 grams for men and 150 to 160 grams for women.

2.1.3 Most of the amyloid deposits seen by microscopy consist of fibrous components, which are -like wrinkled paper-like and Congo red staining strongly positive, showing double suppression under polarized light. A few amyloid deposits are composed of globulin and starch, and may also contain other proteins. Amyloids are mostly deposited in the middle layer and adventitia of the arterial wall, especially on the outer surface adjacent to the adventitia. In severe cases, the middle elastic layer is completely replaced by amyloid, so that the middle layer is weak, vasodilation, microaneurysm formation or Rupture causes bleeding. Onion-like hyperplasia or vitreous deposition can be seen in the inner membrane, which is often accompanied by increased collagen fibers and thickening of the elastic layer in the outer membrane. A few capillaries also have amyloid deposits on the adventitia surface and in their surrounding cavities. In addition, CAA may have senile plaques (SP), neurofibrillary tangles (NFT), and shedding cells in the cerebral cortex. The former two are abundant and widespread, while the latter are selective. Mutual relationship.

2.2 Pathological changes of cerebrovascular disease complicated by CAA 2.2.1 Intracerebral hemorrhage CAA causes more intracranial hemorrhage, which is mostly limited to the cortex and subcortical white matter on both hemispheres, and easily breaks into the subarachnoid space, so it can be combined with the subarachnoid space Hemorrhage or subdural hematoma, which is rare in the ventricle. Hematomas can occur simultaneously or successively in different brain lobes, near superficial regions, especially the occipital lobe, occipital parietal region, or frontal lobe. Most are multiple bleedings and a few are single bleedings. It can be spot, miliary, flaky, or spinal bleeding, and sometimes the bleeding spots can be fused with each other.

2.2.2 TiA and CAA of cerebral infarction can also cause ischemic stroke. Twenty-three CAA patients have been reported, including 13 cases of cerebral infarction, 9 cases of cerebral hemorrhage, and 1 case of dementia. Pathology confirms that amyloid infiltration of cerebral blood vessels can lead to narrowing of the vascular cavity, hyaline degeneration of small arteries, stenosis of intimal hyperplasia, fibrinoid degeneration, and fibrous obstruction. These lesions can cause focal ischemia, infarction, and softening of the cerebral cortex.

3.1CAA mostly occurs in elderly people over 60 years of age, with an average age of onset of 69.5 years old, and the incidence often increases with age. It is often accompanied by Alzheimer's disease. In the literature, 89% of CAA patients have AD, and brain pathological examinations of CAA patients often have senile changes such as senile plaques (SP) and neurofibrillary tangles (NFT), which are sometimes difficult to distinguish from AD. Due to cerebrovascular diffuse amyloidosis and extensive cerebral ischemia, most patients have different degrees of mental disorders and behavioral abnormalities, which are manifested as memory, orientation, computing, comprehensive analysis ability disorders, or hallucinations, and some appear mentally Excited state of exercise or pseudo-paranoid state. Nervous system symptoms include dysphagia, ataxia, muscle spasms, clonics, or generalized convulsions. A few patients show hemiplegia, aphasia, isotropic, increased muscle tone, and pseudobulbar paralysis.

The disease progresses progressively, and may develop into severe dementia, coma, or vegetative state in the later stages. A few patients do not have dementia at an early stage or develop acute dementia after a stroke.

3.2 CAA complicated cerebral hemorrhage CAA is an important cause of normal blood pressure cerebral hemorrhage. The incidence of CAA complicated with cerebral hemorrhage is 2% ~ 9.3%, accounting for 20% of elderly patients with cerebral lobe hemorrhage, 40% of CAA autopsy cases have cerebral hemorrhage, cerebral lobe hemorrhage is the most common manifestation of CAA, CAA is elderly cerebral lobe blood The most common cause of the patient. Most occur in patients with AD symptoms, and a few can also be the first symptoms. Before the onset of blood pressure, the blood pressure was usually normal, and some patients' blood pressure increased to varying degrees. Bleeding tends to flow into the adjacent subarachnoid space, causing headache, nausea, vomiting, stiff neck, positive Krebs sign and other meningeal irritation symptoms. Because the hemorrhage is shallow, it does not break into the ventricular system, so it is mostly unconscious when it starts. A small number of patients can block the cerebrospinal fluid pathway or affect its reabsorption due to bleeding clots, leading to aggravated consciousness caused by hydrocephalus. For multiple intracerebral hemorrhage, the clinical manifestations are more dangerous, and they usually start with coma, hemiplegia, sudden headache, accompanied by nausea, vomiting or mental disorder. If the bleeding is limited, there are obvious localization symptoms: occipital lobe hemorrhage often results in cortical blindness or Anton syndrome (mistaking the imagination as an item to be seen and denying that he is blind).

Temporal and parietal lobe hemorrhage may be blind or quadrant blind. Frontal lobe hemorrhage mainly manifests with mental disorders, such as indifference, lack of desire, forgetfulness, sluggishness, etc., may have groping reflexes and strong grip reflexes. CAA-associated cerebral hemorrhage rarely occurs in non-cerebral lobe sites and therefore does not generally occur in common sites of hypertensive cerebral hemorrhage such as the putamen, thalamus, and pontine, but the cerebellum can have different amounts of vascular amyloid, so it can sometimes be CAA with bleeding site. CAA-induced cerebral hemorrhage is also characterized by a tendency to rebleed months or years later, and even hematomas in different parts. Although CAA often severely involves the meningeal vessels, CAA-related primary subarachnoid hemorrhage is very rare. Lumbar penetrating cerebrospinal fluid pressure increased, showing uniform bloody.

3.3 TiA is the most common CAA-complicated ischemic stroke. It is more common in the internal carotid artery system and can manifest transient anaesthesia, hemiplegia, and named aphasia. It can also be the vertebral-basal artery system TiA, which manifests as transient vertigo, tinnitus, ataxia, and cortical blindness. CAA complicated with cerebral infarction is more common in the occipital lobe, posterior temporal, parietal lobe and frontal lobe, showing corresponding clinical symptoms and signs, but generally smaller than the scope of arteriosclerotic cerebral infarction, the symptoms are milder, but can occur frequently and relapse.

When CAA is complicated by cerebral hemorrhage, the common part is cortex or subcortex. Single or multiple cerebral lobe hemorrhage is shown by CT of the skull. High-density hematoma images can be seen in the occipital lobe, posterior parietal occipital or frontal cortex and subcortex. Signs of secondary subarachnoid hemorrhage. Skull MRI can also show cortical or subcortical spotted hemorrhages, with irregular edges of the hemorrhages, extending to the white matter, and a wide density area around the hematoma. Gradient echo (sensitivity-weighted) MRI provides very useful information for the diagnosis of CAA in elderly patients with cerebral lobe hemorrhage.

5.1 Diagnosis There is no specific diagnostic method for CAA. Most CAA cases are diagnosed only after pathological examination. For patients over 55 years of age, there is no obvious cause of one or more lobe hemorrhages, and the possibility of CAA must be considered. MRI and hematoma removal pathological examination or cerebral cortical biopsy provide two ways to diagnose possible CAA. Based on clinical and radiological data, the diagnostic and probable CAA criteria are as follows (Boston diagnostic criteria for CAA-related cerebral hemorrhage): It must be a full autopsy of the CAA to confirm: (1) cerebral lobe, cortex, or subcortical hemorrhage (2) Severe CAA, accompanied by vascular disease (3) The pathological manifestation of no other disease is likely to be CAA, clinical data accompanied by supporting pathological evidence, and pathological tissue (cleared hematoma or cortical biopsy) confirm: (1) brain lobe , Cortical or subcortical bleeding (2) CAA to some extent (3) no pathological manifestations of other diseases are likely to be confirmed by clinical data from CAA and MRI or CT: (1) recurrent bleeding is limited to the cerebral lobe, cortex or subcortical Area (2) Age 55 years old (3) No other cause of bleeding may be CAA clinical data and MRI confirmation: (1) single blood, located in the cerebral lobe, cortex or subcortical area (2) age 55 years (3) There are no other identified causes of hemorrhage. Clinically for spontaneous intracerebral hemorrhage in elderly patients or dementia patients, especially in the brain Multiple intracerebral hemorrhage and cortical mass, hematoma and soon broke the possibility of subarachnoid hemorrhage should occur due to CAA. The main points of CAA clinical diagnosis can be summarized as follows: (1) more common in old age, especially over 70 years of age; (2) chronic progressive dementia or acute dementia after stroke; (3) non-traumatic, non-hypertensive cerebral hemorrhage, skull CT or MRI refers to the presence of high-density shadows of hematomas in the occipital, temporal, parietal, or frontal or subcortical areas, often breaking into the subarachnoid space. (4) Some patients start with TiA or cerebral infarction. CT or MRI scans on the head can show infarcts in the above areas. (5) Stroke attacks are multiple or recurrent. (6) Pathological examination is of definite significance. The brain tissue biopsy of the arterial wall is stained with Congo red, and the green birefringence reaction under a polarizing microscope can be diagnosed as CAA. 5.2 Differential diagnosis of CAA and AD, Pick's disease, multiple infarct dementia, subcortical arteriosclerotic encephalopathy, and other dementias need to be distinguished from hypertensive cerebral hemorrhage, subarachnoid hemorrhage, and arteriosclerotic cerebral infarction.

6.1 Treatment 6.1.1 Chemicals that inhibit the formation of A and antibodies that increase the clearance of A deposition are being developed. Other potential agents that may prevent rupture of the blood vessel wall from amyloid deposition include A deposition inhibitors, antioxidants and anti-inflammatory properties. Agents are in the clinical trial stage. 6.1.2 Most animal experiments and a few clinical reports apply cytotoxic drugs to treat reactive amyloidosis, which can promote the elimination of subunit particles of powdery substance from urine and control clinical symptoms. The adrenocortical hormone's therapeutic effect is controversial because it can accelerate the deposition of amyloid. 6.1.3 The acute management of CAA complicated cerebral hemorrhage is the same as other cerebral hemorrhage management principles. Hematoma removal or lobectomy can be performed when necessary, but surgical treatment should be prudent. Because amyloid replaces the middle structure of blood vessels, affecting the contraction and hemostasis of blood vessels, it is easy to cause major bleeding. However, for early patients with repeated bleeding, Direct hemostasis and prevent rebleeding can be treated with surgery. 6.1.4 Patients with concurrent TiA or cerebral infarction shall be treated according to the corresponding principles of ischemic stroke, but antiplatelet aggregation drugs, anticoagulants and thrombolytic drugs are prohibited. 6.1.5 People with dementia can apply drugs that promote brain cell metabolism. 6.2 The prognosis of CAA is mostly progressive. The course of disease is 5 to 19 years, with an average of 13.3 years. The age of death is 59 to 72 years, with an average of 65.8 years.

CAA causes high mortality from intracerebral hemorrhage, such as age, physical fitness, hematoma size, and extent of spread. A few surgical treatments to clear the hematoma and medical treatment can stop bleeding.

Imaging Changes of Cerebral Amyloid Vascular Disease (CAA) -related Inflammatory Processes and Their Risk Factors and Course Features

According to KinnecomC, a study published in the April 24, 2007 issue of Neurology revealed imaging changes and risk factors and course characteristics of inflammatory processes associated with cerebral amyloid angiopathy (CAA). KinnecomC et al. Evaluated 14 patients with pathological diagnosis and confirmed CAA-related inflammatory response and found that baselineMRI is characterized by asymmetric T2 high signal changes. The lesion extends to the subcortical white matter, and occasionally involves the gray matter covered above. Signal characteristics suggest Angioedema is present, and the volume of high-signal areas on MRI correlates with the severity of clinical symptoms. As one of the risk factors, the APOE4 / 4 genotype is closely related to the CAA-related inflammatory process. 76.9% (10/13) of the subjects expressed the gene expression and had clinical symptoms but no inflammatory response in CAA patients. The positive rate was only 5.1% (2/39). Subjects can be divided into three groups based on their response to immunosuppressive therapy during the course of the disease: the single-phase improvement group (7/12), the initial improvement group with symptom relief (3/12), and the no-significant response group (2/12) ). Studies have confirmed that this manifestation is symptoms of cognitive impairment, seizures, headaches, etc., T2 high-signal lesions seen on MRI, and CAA-associated changes in CAA-associated vascular inflammation found in neuropathology are related to clinical practice of Alzheimer disease and ongoing immunotherapy .