Amyloid angiopathy — a rare cause of intracerebral hemorrhage

The cerebral amyloid angiopathy (CAA), morphologically characterized by amyloid deposition in the vessel walls which are altered to rigid tubes, is a chronic disease of the cortical and meningeal vessels and can cause intracerebral hemorrhages (1,5% of all intracerebral bleedings). We report the course of five surgically treated patients with lobar space-occupying intracerebral hemorrhages and CAA confirmed by histological examination. All patients were elderly (74–84 years), in good condition, and self-providing before the hemorrhage. There were no signs of dementia of the Alzheimer's type. In four cases, CT showed a hematoma in the parietooccipital, and in one case in the temporo-parietal, region. After surgical evacuation, two patients recovered, one patient remained in bad condition, and two patients died from recurrent hemorrhage within two weeks. Spontaneous intracerebral hemorrhage of lobar localisation in an elderly patient strongly suggests CAA. The prognosis seems to be poor in cases with recurrent hemorrhage, the other patients presented an uneventful course, comparable with patients operated on for intracerebral bleeding of other origin. Further investigations are necessary to elucidate the prognosis of this entity.     

Cerebral hemorrhage from amyloid angiopathy and coronary thrombolysis.

Coronary thrombolysis with streptokinase or tissue plasminogen activator is useful for the treatment of acute myocardial infarction in selected patients. This treatment is associated with local hemorrhagic complications and age-related cerebral hemorrhage. Coronary thrombolysis is contraindicated in patients with transient cerebral ischemia and stroke, arterial hypertension, cerebral trauma, cerebral aneurysms, and arteriovenous malformations, because of the risk of cerebral hemorrhage. We report the occurrence of a cerebral hemorrhage related to cerebral amyloid angiopathy in a patient who underwent thrombolysis and treatment with heparin for acute myocardial infarction. Despite normal coagulation parameters, the cerebral hematoma enlarged over 36 hours, as documented by sequential computed tomographic scans, to produce significant mass effect, which prompted surgical evacuation. Histological examination of the resected specimen demonstrated the strong affinity for Congo red and yellow-green birefringence that are characteristic of cerebral amyloid angiopathy. Hemostasis was difficult to achieve, as the divided or disrupted amyloid-laden cortical vessels failed to vasoconstrict, their contractile elements replaced by amyloid beta protein. The patient died of recurrent myocardial ischemia 3 days postoperatively. The incidence of cerebral amyloid angiopathy increases with advancing age. It must be considered as a potential source of cerebral hemorrhage in elderly patients undergoing thrombolysis for cardiac ischemia. Such an occurrence presents a difficult challenge because cardiac function is compromised, the coagulation profile may be altered, the cerebral hematoma is life threatening, and intracranial hemostasis is difficult to achieve.     

A restricted subarachnoid hemorrhage in the cortical sulcus in cerebral amyloid angiopathy: could it be a warning sign?

BACKGROUND: Cerebral amyloid angiopathy is a well-known disease that is predominantly recognized in elderly people and repeatedly causes large subcortical hemorrhages. These hemorrhages may be derived from vessel wall weakness because of Abeta depositions in the wall of the cortical and leptomeningeal arteries. Although vessel ruptures in CAA have been thought to occur in cortical arteries, it was recently demonstrated that the primary hemorrhage occurs in the subarachnoid space, particularly the cerebral sulci, as a result of multiple ruptures of meningeal arteries in some cases of subcortical hematoma caused by CAA. CASE DESCRIPTION: Case patient 1 was a 74-year-old woman who presented with epileptic seizure. A restricted SAH in the right frontal lobe was observed on MRI. Thirty-three days later, left hemiparesis occurred suddenly and a huge subcortical hematoma was observed in the right frontal lobe on CT. The hematoma was removed, and the patient was pathologically diagnosed with amyloid angiopathy. Case patient 2 was a 73-year-old man who presented with epileptic seizure. A restricted SAH in the right frontal lobe was observed on MRI. Twenty days later, left hemiparesis occurred suddenly and a huge subcortical hematoma was observed in the right frontoparietal area on CT. Hematoma removal was performed on both patients, and they were diagnosed pathologically with amyloid angiopathy. CONCLUSIONS: We report on the cases of 2 patients with CAA who presented with epileptic seizure and were found to have a restricted subarachnoid hematoma in the cerebral sulcus on MRI before their subcortical hemorrhages occurred. Both cases were diagnosed pathologically. This demonstrated that vessel ruptures in CAA can occur in the subarachnoid space, particularly the cerebral sulci, as a result of ruptures of meningeal arteries. A restricted SAH on CT/MRI could be a warning sign of a huge subcortical hemorrhage in CAA.     

Multiple intracerebral hemorrhages due to cerebral amyloid angiopathy after head trauma

Cerebral amyloid angiopathy (CAA) is an important cause of intracerebral hemorrhage and ischemic cerebrovascular disease in some normotensive elderly patients. The diagnosis is made by proof of amyloid deposition in the vessel wall. A case of recurrent and multiple intracerebral hemorrhages due to cerebral amyloid angiopathy after head injury is reported. A 74-year-old female was referred to our hospital because of head injury. CT scan showed traumatic subarachnoid hemorrhage and intraventricular hematoma. Her consciousness was clear but slight disorientation was recognized. Conservative therapy was performed. During the course subcortical hemorrhages occurred five times and during the second one, right frontal and right parietal hemorrhages occurred simultaneously. Her consciousness deteriorated. The second subcortical hemorrhage was especially complicated by a ventriculoperitoneal shunt operation. A biopsy of the cortex was performed and pathological examination revealed amyloid deposition in the walls of small pial and cortical vessels. Occasional duplicated wall, obliterative intimal proliferation and disappearance of elastic lamina were recognized. The patient sank into a vegetative state due to recurrent and multiple hemorrhages. CAA results in two possibilities, hemorrhage and ischemic cerebrovascular disease. When lobar or subcortical hemorrhage is encountered in a normotensive elderly patient, the possibility of a CAA-related hemorrhage should be considered. The author carefully emphasizes that there is indication for neurosurgical treatment in CAA patients and proposes that therapy for ischemic cerebrovascular disease should be given special attention.     

Cerebral amyloid angiopathy complicated by multiple cerebral infarcts and intracerebral hemorrhages: case report

Recently, cerebral amyloid angiopathy is stressed as an unusual and infrequent cause of cerebral infarct or intracerebral hemorrhage. This report described a case of cerebral amyloid angiopathy complicated by multiple cerebral infarcts and multiple intracerebral hemorrhages. This 70-year-old man was admitted to our hospital on November 10, 1984 for evaluation of the gradual onset of dysarthria. Examination showed only slight dysarthria. There was no history of hypertension or dementia. A computed tomography (CT) showed enlarged ventricles with cortical atrophy and multiple low-density lesions, deep in the left frontal, left parietal, right parietal lobes, and in the both basal ganglias. The patient discharged from the hospital with only slight dysarthria. On November 20, 1984, he was admitted to our hospital again, because he was found unresponsive on the floor. He was somnolent but arousable. Examination showed disorientation, impairment of recent memory and impairment of calculation, A CT scan demonstrated three small intracerebral hemorrhages in the left frontal, right parietal lobes and left basal ganglia. On the fifth hospital day he deteriorated acutely, becoming semicomatose and hemiparetic on the right side. A repeated CT scan showed two new intracerebral hemorrhages in the left frontal lobe. Cerebral angiograms showed only minimal changes due to the occupying lesions in the above mentioned area. The hematomas was evacuated via left fronto-parietal craniotomy. The specimens removed with hematoma (stained with hematoxylin-eosin, Congo red and thioflavin T) showed extensive amyloid angiopathy. Postoperatively he made a good recovery, although he had residual mental dysfunctions. He expired by pneumonia on March 30, 1985.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intracerebral hemorrhage due to cerebral amyloid angiopathy. Case report

The case is presented of a 59-year-old man with cerebral amyloid angiopathy and three consecutive hemorrhages in the occipital lobes. The clinicopathological features and the relationship to Alzheimer's dementia are discussed. The correct treatment of intracerebral hemorrhage related to cerebral amyloid angiopathy is a matter of controversy.     

The incidence of cerebral amyloid angiopathy in surgically treated intracranial hemorrhage in the Chinese population

Despite being widely accepted as an important cause of spontaneous intracranial hemorrhage (ICH), cerebral amyloid angiopathy (CAA) has seldom been studied in the Chinese population. The current study aims to investigate the incidence and features of CAA in surgically treated ICH patients in China. From May 2006 to April 2011, 974 patients admitted to 71 hospitals throughout China for acute spontaneous ICH were studied. Craniotomy for hematoma evacuation was performed. Brain tissue from the superficial side of the suspected residual hematoma cavity, as well as from the cortex and subcortex, was obtained. Congo Red stain and β-amyloid immunohistochemistry were used for the diagnosis. Each case was assigned a pathological severity score. Of the 974 involved patients, 37.7 % were identified with CAA of different degrees. CAA had positive correlation with age and was independent of sex. Most patients had mild CAA with only the superficial vessels involved in lobes instead of the basal ganglia; the patients ≥65 years had more severe pathological score of CAA than those <65 years and had more lobes and cerebellum involved than the latter. More than one third of the surgically treated Chinese ICH patients may have CAA of different degrees.     

Lobar intracerebral hemorrhage. A clinical, radiographic, and pathological study of 29 consecutive operated cases with negative angiography.

The authors operated consecutively on 50 patients with lobar intracerebral hemorrhage during a prospectively designed study period from January, 1986, to March, 1990. They investigated the correlations between the underlying causes and the clinicoradiographic features in 29 patients who showed no angiographic vascular abnormalities, in order to elucidate the operative indication for such cases. Patients with ruptured saccular aneurysm or trauma were not included in this study. There were 15 males and 14 females, ranging in age from 7 to 76 years (mean 52.4 years). Histological diagnoses of the surgical specimens were as follows: vascular malformation in nine cases (arteriovenous malformation (AVM) in six and cavernous malformation in three), microaneurysm in 11, cerebral amyloid angiopathy in six, and brain tumor in two; in the remaining case the cause was not verified histologically. The underlying cause was determined in 96.5% of cases. The mean patient age was lowest in the cavernous malformation group (27.0 years), followed by the AVM (45.8 years), microaneurysm (59.8 years), and cerebral amyloid angiopathy (70.0 years) groups. Four patients with vascular malformation (three AVM's and one cavernous malformation) had previous episodes of bleeding at the same site, whereas none of those with microaneurysms or cerebral amyloid angiopathy had such episodes. On computerized tomography (CT) scans, the round to oval hematoma was related to the presence of an AVM or cavernous malformation in contrast to microaneurysms and cerebral amyloid angiopathy. Upon infusion of contrast material, variable enhancement was seen in five (two AVM's and three cavernous malformations) of the nine vascular malformations while no enhancement was noted in any patient with microaneurysm or cerebral amyloid angiopathy at the acute stage. Subarachnoid extension of the hematoma was associated with cerebral amyloid angiopathy significantly more frequently than with AVM's (p less than 0.05) and microaneurysms (p less than 0.01). The results suggest that clinicoradiographic pictures in cases with negative angiography are quite different among the three major pathological categories; namely, vascular malformation (AVM and cavernous malformation), microaneurysm, and cerebral amyloid angiopathy. It is suggested that the underlying etiology of a given lobar intracerebral hemorrhage with negative angiography may be predicted by a combination of patient age, history of previous bleeding at the same site, hematoma shape, and subarachnoid extension of the hematoma on CT scans. Based upon these findings, the authors discuss operative indications for such cases.     

Simultaneous, bilateral hypertensive intracranial hematomas

The reported incidences of bilateral intracerebral hemorrhages due to systemic arterial hypertension are exceptionally rare in Japan. Unilateral hemorrhages, on the other hand, are less uncommon. Recently, we have examined two patients with bilateral intracerebral hemorrhages due to hypertension. The first case involved bilateral thalamic hemorrhages; and in the other, a contralateral hemorrhage developed postoperatively, subsequent to the evacuation of a primary hematoma. The characteristic neurological manifestation of bilateral intracerebral hemorrhages include quadriparesis, bilateral Babinski's signs, stupor, and coma. Published information regarding the anatomy of intracerebral hemorrhages due to hypertension is inconclusive, but the bilateral basal ganglias are believed to be most frequently involved. One school of thought explains the pathomechanism of bilateral hemorrhages as a symmetrical rupture of cerebral microaneurysm. However, it is possible that an unilateral hematoma was formed by a ruptured microaneurysm, and subsequently, a contralateral hemorrhage developed in relatively short time due to circulatory disturbance. As in the case of general cerebral hemorrhage, a craniotomy is also indicated for hypertensive bilateral intracerebral hemorrhage.     

CT-guided stereotactic fibrinolysis of spontaneous and hypertensive cerebellar hemorrhage: long-term results

The surgical indication for spontaneous cerebellar hemorrhage is not as controversial as the operative management of intracranial hemorrhage. Timing of the operation is crucial: intervening too early can produce an additional strain on the patient and an increased risk, while waiting too long to evacuate the hematoma can be fatal. This dilemma may be a factor in the relatively high mortality and morbidity rates following both operative and conservative treatment that have been reported in the literature (42.5% and 30%, respectively). In long-term studies on 14 patients, the authors have shown that stereotactic puncture and fibrinolysis for cerebellar hemorrhage is a valuable alternative to treatments used currently. The method consists of computerized tomography (CT)-guided stereotactic puncture and partial evacuation of the hematoma. After fibrinolysis with urokinase, the residual hematoma can be completely evacuated via a catheter introduced into the cavity of the hematoma. Only one of the 14 patients died in the direct postoperative phase; the remaining patients were enjoying a good to very good quality of life 6 months after the acute event. Two patients subsequently died as a result of pneumonia and cerebral infarction, respectively; both conditions were unrelated to the hemorrhage. The authors conclude that the CT-guided stereotactic method is simple, effective, and safe, and can be applied to patients of any age.     

Endoscopic hematoma evacuation for hypertensive cerebellar hemorrhage.

OBJECT: The management of spontaneous cerebral hemorrhage remains controversial, particularly the surgical indications. Endoscopic surgery was evaluated for the treatment of spontaneous cerebellar hemorrhage. METHODS: The records of 69 patients with hypertensive cerebral hemorrhage were retrospectively reviewed. Patients treated by endoscopic surgery (n = 10) were compared with patients treated by conventional surgical hematoma evacuation (n = 10) under the same surgical indications. RESULTS: The surgical procedure time, duration of ventricular drainage, extent of hematoma evacuation, necessity for cerebrospinal fluid (CSF) shunt, surgical complications, and outcome at discharge and at 3 months after onset were compared. The extent of hematoma evacuation was greater in the endoscopic group (95.2 %) than in the craniectomy group (90.6 %) but without significant difference. The endoscopic technique (64.5 min) took significantly less time than the craniectomy method (230.6 min, p < 0.0001). The period of ventricular drainage was significantly shorter in the endoscopic group (2.6 days) compared to the craniectomy group (12.3 days, p < 0.01). CSF shunt surgery was required in no patient in the endoscopic group compared to three in the craniectomy group. CONCLUSION: Endoscopic hematoma evacuation is a rapid, effective, and safe technique for the removal of hypertensive cerebellar hemorrhage. Reduction of the mass effect can be accomplished with low risk of recurrent hemorrhage. Release of obstructive hydrocephalus in the early stage may improve the patient's outcome and decrease the requirement for permanent shunt emplacement.     

Cerebral amyloid angiopathy associated with hemorrhage: immunohistochemical study of 41 biopsy cases.

The relationship between cerebral amyloid angiopathy and hemorrhage was investigated by an immunohistochemical study of biopsy cases to characterize the involvement of amyloid beta-protein, apolipoprotein E, and cystatin C in cerebral amyloid angiopathy associated with hemorrhage. The amyloid-laden vessels were examined in biopsy specimens from 41 surgical cases of sporadic cerebral amyloid angiopathy (36 cases with hemorrhage and 5 cases without hemorrhage), using immunohistochemical staining with antibodies against amyloid beta-protein, apolipoprotein E, cystatin C, and alpha-smooth muscle actin. The relationship between the occurrence, recurrence, and enlargement of the hemorrhage, and the semiquantitative estimation of the cerebrovascular amyloid-related protein deposition was analyzed using Fisher's exact test. Severe amyloid beta-protein (p < 0.013) and apolipoprotein E (p < 0.013) immunoreactivity were risk factors for the occurrence of the hemorrhage. Severe cystatin C immunoreactivity was a risk factor for the occurrence (p < 0.002) and enlargement (p < 0.014) of the hemorrhage, and tended to induce recurrent hemorrhage (p < 0.103). In addition, loss of the vascular smooth muscle was observed in the intensely amyloid-laden vascular walls that showed cystatin C-immunoreactivity. The present study indicates that intense amyloid beta-protein deposition with cystatin C deposition weakens the cerebrovascular walls, and that cystatin C deposition is a strong predictor of hemorrhage in cerebral amyloid angiopathy.     

Modern treatment options for intracerebral hemorrhage

Opinion statement Spontaneous intracerebral hemorrhage (ICH) is a devastating neurological event with a 30-day mortality of approximately 40%. Recent research provides new insights into the pathophysiology of ICH-associated edema, with potential molecular and cellular targets for future therapy. Neuroimaging techniques such as gradient echo MRI are yielding insights into cerebral microbleeds and the microangiopathies associated with hypertension and cerebral amyloid angiopathy. Recent literature provides new medical treatment strategies for fever, acute hypertension, and perihematomal edema, and methods of reducing intracranial pressure. Two randomized controlled trials have provided crucial evidence regarding surgical and medical intervention for acute ICH intervention. Recombinant factor VIIa appears to lessen growth of ICH when administered within 4 hours of ictus. Further study of potential efficacy and safety is underway in an international phase III trial. In addition, the Surgical Trial in Intracerebral Hemorrhage reported results from an international randomized trial of 1033 patients who did not show benefit for surgical evacuation of ICH, compared with medical therapy alone. Less invasive surgical methods for hematoma evacuation, studied previously over the past decade, continue to be investigated.     

Recurrence and extension of lobar hemorrhage related to cerebral amyloid angiopathy: multivariate analysis of clinical risk factors

BACKGROUND: Many recent studies have analyzed clinical risk factors for the recurrence and extension of intracerebral hemorrhage. However, they have not been investigated in patients with lobar hemorrhage related to cerebral amyloid angiopathy (CAA). METHODS: We studied 40 surgically treated patients with lobar hemorrhage diagnosed histologically as being related to CAA. To determine clinical factors influencing the recurrence and hematoma size their clinical data (demographics, medical history, and radiographic and laboratory data) were examined retrospectively and subjected to multivariate analysis. RESULTS: Twelve patients (30%) had recurrent lobar hemorrhage. Twenty-one patients had a small hematoma and 19 had a large hematoma. Hypertension was the only significant clinical factor influencing the recurrence of CAA-related lobar hemorrhage. There was no significant clinical factor influencing the hematoma size of CAA-related lobar hemorrhage. CONCLUSIONS: The history of hypertension is associated with an increase in the recurrence of CAA-related lobar hemorrhage.     

Outcome of cerebral amyloid angiopathic brain haemorrhage

Background  Abnormal amyloid protein can be deposited in the wall of cerebral arteries leading to fragility and intracerebral haematoma in patients with cerebral amyloid angiopathy. Diagnosis can be done only histologically. The indication of surgically treating intracerebral haemorrhage caused by amyloid angiopathy is controversial. There are studies showing a high mortality and a high rate of recurrent bleeding. Others show almost no recurrent bleeding and a very low mortality and a third party states that even when recurrent intracerebral haemorrhage occurs, re-evacuation should be performed. In the present retrospective study a population of 99 patients suffering from cerebral amyloid angiopathy-related cerebral haemorrhage has been studied, to investigate the surgical outcome. Method  Ninety-nine patients were histologically diagnosed with cerebral amyloid angiopathy in our department from 1991–2004. The outcome has been established by the Glascow Outcome Score. Findings  It could be shown that intraventricular bleeding and age >75 years increased the mortality after operative evacuation. Recurrent bleeding occurred in 22% of patients. After re-evacuation at least half of the patients survived leading to the suggestion to re-operate a recurrent bleeding since patients have a chance to survive even when the Glascow Outcome Score is 3. The overall mortality in the observed population was 16% and 11% had a very good neurological recovery based on a Glascow Outcome Score of 4–5. The operative outcome in amyloid angiopathy related intracerebral haemorrhage is similar to this of intracerebral haemorrhage induced by other causes like hypertensive bleeding. Conclusions  Possible cerebral amyloid angiopathy is no contraindication for evacuation of brain-haematoma, and especially not in patients younger than 75 years old without an intraventricular haemorrhage.     

Clinical and cerebral blood flow studies in patients with intracranial hemorrhage and amyloid angiopathy typical of Alzheimer's disease

Spontaneous intracerebral hemorrhages can occur in patients with severe amyloid angiopathy and other morphological signs of Alzheimer's disease (AD). We observed 15 patients in whom histological examination of brain tissue specimens obtained at surgery revealed characteristic congophilic amyloid deposits in subcortical arteries and/or nerve cells. Clinical follow-up examinations were carried out up to 9 years after diagnosis. In addition, three survivors from the operated group were investigated by neuropsychological testing and single photon emission computer tomography (SPECT) using Tc-99m-HMPAO for determination of regional cerebral blood flow (rCBF).SPECT could not differentiate between the typical Alzheimer disease pattern of bilateral temporo-parietal rCBF reduction and flow deficits resulting from previous hemorrhage. Intellectual functioning was found to be impaired to various degrees ranging from normal function to severe dementia (MMS test scores varied between 15 and 26 points); again, it was difficult to differentiate clinically between the nosologic entities mentioned above.On the basis of our present experience we cannot distinguish between brain dysfunction due to Alzheimer's disease and intracranial hemorrhage from amyloid angiopathy. This supports the idea that intracranial hemorrhage may only be one clinical manifestation of amyloid deposits, another one being Alzheimer's disease with varying preponderance.     

Recurrent intracerebral hemorrhages in cerebral amyloid angiopathy: a case report

Cerebral amyloid angiopathy frequently causes recurrent intracerebral hemorrhages in elderly patients who do not have systemic hypertension. Surgery should be reserved for conditions which cannot be controlled by medical treatment. When surgery is needed, potential complications (such as bleeding near the operation site or remote area) should be kept in mind. A case study of a 66-year-old woman with cerebral amyloid angiopathy and recurrent intracerebral hemorrhages is presented.     

Cerebral amyloid angiopathy presenting as multiple intracranial lesions on magnetic resonance imaging. Case report

Cerebral amyloid angiopathy is recognized as an important cause of spontaneous intracerebral hemorrhage in the elderly normotensive patient. Magnetic resonance (MR) imaging characteristics of this disease entity are rarely mentioned in the literature. The MR imaging findings of an elderly normotensive patient presenting with an acute spontaneous intracerebral hemorrhage secondary to amyloid angiopathy are reported and a brief review of amyloidosis is presented.     

Neurosurgical and immunological implications of primary cerebral amyloid (congophilic) angiopathy

Two cases of histologically documented primary cerebral amyloid complicated by spontaneous intracerebral hematoma are reported. The neurosurgical implications of this disease are reviewed briefly. Immunological studies in one patient, believed to be a rare survivor of an intracerebral hemorrhage from nonfamilial primary cerebral amyloid angiopathy, demonstrated an increased percentage of B cells within both the cerebrospinal fluid (CSF) and the blood compartments. Hypofunction of CSF concanavalin A-activated suppressor cells with respect to B and T cell targets was shown. The blood suppressor cells from the patient were similar to those of an age-matched control. Compartmental central nervous system suppressor cell dysfunction resulting in B cell activation could play a role in facilitating amyloid deposits in the brain. The mechanisms responsible for the compartmental and limited suppressor cell dysfunction are unknown.