Loss of vessel wall viability in cerebral amyloid angiopathy

Cerebral amyloid angiopathy (CAA) is a neuropathological feature of Alzeheimer's disease and an important cause of cerebral haemorrhage in the elderly. CAA is characterized by the deposition of Alzheimer amyloid beta protein (A beta) in cerebral and leptomeningeal vessel walls. In order to study the effect of cerebrovascular A beta deposits in vivo, living canine leptomeninges obtained from old dogs affected by CAA were analysed by confocal laser scanning microscopy after immunofluorescence staining for A beta and viability staining with fluorescein diacetate (FDA). Simultaneous detection of the two signals showed a segmental loss of leptomeningeal vessel wall viability at some site of A beta deposition. Many of the non-viable vessels segments were also dilated, suggesting that A beta-induced vascular cell death creates the loci minores resistentiae for the development of cerebral haemorrhage in CAA.     

Microvasculopathy is associated with the number of cerebrovascular lesions in hereditary cerebral hemorrhage with amyloidosis, Dutch type

BACKGROUND AND PURPOSE: Microvascular changes such as microaneurysms and fibrinoid necrosis have been found in the presence of cerebral amyloid angiopathy (CAA). These CAA-associated microvasculopathies (CAA-AM) may contribute to the development of CAA-associated hemorrhages and/or infarcts, hereafter referred to as "cerebrovascular lesions." Hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D) is an autosomal dominant form of CAA, in which the amyloid angiopathy is pathologically and biochemically similar to sporadic CAA associated with aging and Alzheimer disease. To determine the significance of CAA-AM for CAA-associated cerebrovascular complications, we investigated the association between CAA-AM and cerebrovascular lesions in HCHWA-D patients. METHODS: In a previous autopsy study we semiquantitatively scored CAA-AM in 29 HCHWA-D patients. In the present study we reviewed clinical charts and autopsy protocols of these same patients. We investigated whether CAA-AM was associated with age at death, number of cerebrovascular lesions, duration of clinical illness, hypertension, and atherosclerosis. RESULTS: An association was found between CAA-AM and the number of cerebrovascular lesions (P = 0.009). The presence of microaneurysmal degeneration was most strongly associated with the number of cerebrovascular lesions (P < 0.001). In addition, we found an association between atherosclerosis and the CAA-AM score (P = 0.047). Hypertension was not associated with CAA-AM. CONCLUSIONS: Our findings support previous reports suggesting an important role of secondary microvascular degenerative changes in CAA-associated cerebrovascular lesions and suggest an aggravating effect of systemic atherosclerosis, but not hypertension, on the evolution of CAA-AM. These findings may be of relevance to understanding cerebrovascular complications of sporadic or Alzheimer disease-associated CAA.     

Bleeding following tracheostomy: the brachiocephalic trunc

Life threatening haemorrhage following lesions of the great supraaortic vessels has to be expected after tracheostomy in a ratio of 1:150. 0.6 to 1.1% of these lesions involve the brachiocephalic trunc. In most cases the acute haemorrhage can be controlled by hyperinflation of the cuff of the endotracheal tube. The following immediate emergency operation consists of ligature or resection of the brachiocephalic trunc. No cerebral damage is to be expected afterwards. The indication for vascular reconstruction of the trunc should be considered as a secondary matter.     

Butyrylcholinesterase K variant and cerebral amyloid angiopathy

BACKGROUND and PURPOSE: Cholinesterases are found histochemically in the vessels affected with cerebral amyloid angiopathy (CAA). A gene for the K variant of butyrylcholinesterase (BCHE-K) may be associated with late-onset Alzheimer's disease (AD). In search of genetic risk factors for CAA, we investigated the association of BCHE-K with CAA. METHODS: The association between the severity of CAA and BCHE-K was investigated in 155 autopsy cases of the elderly, including 48 patients with AD. RESULTS: There was no significant association of BCHE-K with the severity of CAA in the total, AD, or non-AD cases. Status of the epsilon4 allele of apolipoprotein E gene did not influence the results. CONCLUSIONS: Our results may suggest that BCHE-K is not a definitive risk factor for CAA in the elderly, although further study with larger samples is necessary to confirm this.     

Role of the pneumo-encephalogram in the diagnosis of spontaneous subarachnoid haemorrhage

The authors have collected eighteen cases of primary intraventricular lesions revealed by a subarachnoid haemorrhage. Among these cases, the most important are the choroid plexus papillomas followed by ependymomas; some cases have no precise histological interpretation. Generally speaking, cerebral arteriography gives only indirect evidence of ventricular dilation and thus does not confirm the presence of a lesion. On the contrary, the pneumoencephalogram is consistantly positive, but does not give the differential diagnosis between intraventricular tumours and primary intraventricular haemorrhages. This test should therefore be given the same importance as spinal cord arteriography in the exploration of subarachnoid haemorrhages with negative cerebral angiograms.     

Animal models of cerebral beta-amyloid angiopathy

Cerebral amyloid angiopathy (CAA) is a significant risk factor for hemorrhagic stroke in the elderly, and occurs as a sporadic disorder, as a frequent component of Alzheimer's disease, and in several rare, hereditary conditions. The most common type of amyloid found in the vasculature of the brain is beta-amyloid (A beta), the same peptide that occurs in senile plaques. A paucity of animal models has hindered the experimental analysis of CAA. Several transgenic mouse models of cerebral beta-amyloidosis have now been reported, but only one appears to develop significant cerebrovascular amyloid. However, well-characterized models of naturally occurring CAA, particularly aged dogs and non-human primates, have contributed unique insights into the biology of vascular amyloid in recent years. Some non-human primate species have a predilection for developing CAA; the squirrel monkey (Saimiri sciureus), for example, is particularly likely to manifest beta-amyloid deposition in the cerebral blood vessels with age, whereas the rhesus monkey (Macaca mulatta) develops more abundant parenchymal amyloid. These animals have been used to test in vivo beta-amyloid labeling strategies with monoclonal antibodies and radiolabeled A beta. Species-differences in the predominant site of A beta deposition also can be exploited to evaluate factors that direct amyloid selectively to a particular tissue compartment of the brain. For example, the cysteine protease inhibitor, cystatin C, in squirrel monkeys has an amino acid substitution that is similar to the mutant substitution found in some humans with a hereditary form of cystatin C amyloid angiopathy, possibly explaining the predisposition of squirrel monkeys to CAA. The existing animal models have shown considerable utility in deciphering the pathobiology of CAA, and in testing strategies that could be used to diagnose and treat this disorder in humans.     

Behcet's disease with pulmonary vessel involvement

The case of systemic vasculitis with involvement of pulmonary vessels was described. 36-years white woman with cerebral vasculitis and recurrent uveitis 5 and 3 years ago, now was admitted to hospital because of the mouth ulceration and lesions in the chest x-ray. After lung cancer exclusion, aneurysm of pulmonary artery branch was confirmed by dynamic tomocomputer examination All mentioned above manifestations were diagnosed as Behcet disease. Patient was treated with prednison, cyclophosphamide and cyclosporine. Clinical effect was observed after corticotherapy, but no improvement in chest X-ray picture was obtained also after immunosuppression. Patient died because of pulmonary haemorrhage 7 years after first symptoms of vasculitis and 2 years after first massive haemorrhage.     

Cardiac myocyte membrane wounding in the abruptly pressure-overloaded rat heart under high wall stress

A case of perimesencephalic non-aneurysmal subarachnoid haemorrhage is reported. The patient was a 54-year-old women, after spontaneous subarachnoid haemorrhage with negative cerebral angiography. Internal hydrocephalus due to haemorrhage developed and ventriculo-atrial shunt was inserted. Outcome is presented and the possible causes of bleeding are discussed.     

Cerebral amyloid angiopathy

Cerebral amyloid angiopathy affects the cerebral vasculature selectively, and there is no systemic amyloidosis. Amyloid is deposited in small and medium-sized vessels of the cortex and leptomeninges. Cerebral amyloid angiopathy is a common cause of spontaneous lobar haemorrhage in elderly patients. However, cerebral amyloid angiopathy may have atypical clinical and radiological presentations. We report on five patients (three males and two females, aged 43-77 years) with histologically verified cerebral amyloid angiopathy. One patient experienced an acute headache attack and classical lobar haemorrhage. The other patients had various neurological symptoms and signs, such as seizure, disturbed vision, pareses, aphasia, and dementia that were initially diagnosed as cerebral infarction or tumour. Two patients with cerebral amyloid angiopathy and granulomatous angiitis responded to immunosuppressive treatment.     

Effect of cerebral ischaemia on the cerebrovascular and cardiovascular response to haemorrhage

Reports studying the combination of low blood pressure and cerebral ischaemia are few, and it remains to be determined how cerebral circulatory insufficiency modifies the cerebral perfusion and the central haemodynamic response to blood loss. We hypothesised that occlusion of arteries to the brain modifies the cerebrovascular and cardiovascular responses to blood loss. Continuous measurements of the cerebral microcirculation with laser Doppler microprobes in the cerebral cortex were performed in anaesthetised pigs during cerebral ischaemia and haemorrhagic hypotension. The response to rapid bleeding (25% of the blood volume) was recorded during normal conditions and during cerebral ischaemia induced by bilateral occlusion of the common carotid arteries. During normal conditions haemorrhage caused insignificant decreases in cerebral microcirculation. Haemorrhage during bilateral carotid artery occlusion, however, caused significantly greater changes in cerebral microcirculation and a greater posthaemorrhagic increase in cerebrovascular resistance shortly after the blood loss. Haemorrhage during bilateral carotid artery occlusion also caused greater reductions in cardiac output and arterial pressure than similar blood loss caused during normal conditions. This study showed a disproportionate decrease in cerebral blood flow with haemorrhage during bilateral carotid occlusion, caused by an immediate increase in cerebrovascular resistance. The results suggest that even a moderate blood loss in patients with impaired cerebral circulation could be dangerous, because normal compensatory mechanisms to haemorrhage are impaired.     

Respiratory-chain and pyruvate metabolism defects: Italian collaborative survey on 72 patients

Cerebral amyloid angiopathy (CAA) is a neuropathological feature of Alzheimer's disease and a common cause of cerebral hemorrhage in the elderly. The pathogenetic mechanisms leading to the deposition of Alzheimer amyloid beta-protein (A beta) in cortical and leptomeningeal vessel walls are unknown. There are no experimental models which reproduce the pathological changes of CAA. In this study, leptomeninges from young and old dogs with pre-existing CAA were cultured in cell culture medium or cerebrospinal fluid and their viability, histological appearance and metabolic activity were analyzed during the culture. In addition, living leptomeninges of old and young dogs were incubated with fluorescein-conjugated A beta and the uptake of A beta was studied by fluorescence microscopy. Leptomeninges from young and old dogs were viable up to 8 weeks in culture. They contain many small- and medium-sized arterioles, the main vessel type affected by CAA. Histology and immunohistochemistry showed excellent preservation of the vessel wall microarchitecture up to 4 weeks in culture. The cultures were metabolically active as shown by the de novo production of beta-amyloid precursor protein. Exogenously added A beta was focally deposited in the vessel walls of old, but not young dogs. In conclusion, the organ culture of canine leptomeninges is easy to perform and appears suitable to investigate the pathogenesis and the progression of CAA.     

A 67-year-old woman with polymyalgia rheumatica and left hemispatial neglect

We report 8 patients with the acquired immunodeficiency syndrome (AIDS) and intracerebral haemorrhage. There were 7 men and 1 woman (mean age 37.2 years) with a mean CD4 count of 81.2/mm3. Alcohol abuse was recorded in 7 patients, intravenous drug use in 4, homosexual activity in 2, thrombocytopaenia in 1 and severe hypertension in 1. There were 5 lobar and 3 deep haemorrhages. Potential aetiologies of intracerebral haemorrhage included cerebral toxoplasmosis (n = 2), thrombocytopenia (n = 2), hypertension (n = 1) and cerebral tuberculosis (n = 1). Data of these patients were compared with those of 30 AIDS inpatients without brain haemorrhage matched by age and sex and no statistically significant differences in risk factors for AIDS except for alcohol abuse (> 80 g/day) (p = 0.045) were found. Causes of brain haemorrhage in AIDS patients are heterogeneous. The relationship between both conditions may be explained by the effect of several predisposing factors to stroke in association with AIDS-related complications. Intracerebral haemorrhage is a late and serious complication of AIDS (mortality 62.5%). The frequency of intracerebral haemorrhage in AIDS (1.0%) is higher than that expected in a general population of young adults.     

Evaluation of serum lipid profile and cardiac enzyme changes in cerebrovascular accidents

Serum lipid profile is, total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL) and triglycerides and serum cardiac enzymes ie, creatinine phosphokinase (CPK), creatinine phosphokinase isoenzyme MB (CPK-MB), lactate dehydrogenase (LDH) and serum aspartate aminotransferase (AST/SGOT) levels were estimated in 50 cases of cerebrovascular accidents (CVA) consisting of 26 cases of cerebral haemorrhage and 24 cases of cerebral thrombosis. All analyses were made on day 1 and day 7. Serum cholesterol, LDL and triglycerides levels were significantly higher in CVA patients on day 1. Lipid level fell significantly on day 7 in respect to day 1. On comparing the lipid levels between cerebral haemorrhage and cerebral thrombosis, no significant difference was observed. Cardiac enzymes like CPK and CPK-MB were significantly raised whereas, AST/SGOT and LDH were marginally raised on day 1 in CVA patients. However, there was no change in cardiac enzyme levels between cerebral haemorrhage and cerebral thrombosis patients.     

Reflexes in brain-dead patients

We report on a patient who suffered an acute, extensive intracerebral haemorrhage, leading to symptoms of cerebral herniation within a few hours. The clinical diagnosis of brain death was made based on a neurological examination, and an apnoea test eight hours after the haemorrhage. A few hours later the diagnosis was changed, as several reflexes reappeared. After six days mechanical ventilation was withdrawn, as the brain damage was considered so serious as to render further therapy futile. It was considered unethical to sustain therapy for a possible organ donation at a later date. A review of relevant the literature, however, shows that brain-dead patients may exhibit such varying degrees of autonomic and spinal reflexes as to cause confusion, thus delaying the physician in making a diagnosis. Often, an opportunity for organ donation is lost. Based on this review, we believe that our patient was indeed brain dead when the first diagnosis was made, and that a cerebral angiography should have been performed. Because organ donation is an important issue, the diagnosis of brain death must be definitive.     

Cerebral amyloid angiopathy. A review

Cerebral amyloid angiopathy (CAA) is a condition characterized by amyloid deposition in cerebral blood vessels. It occurs most frequently in association with clinical Alzheimer's disease but also occurs in some nondemented elderly people. CAA is a cause of spontaneous cerebral hemorrhage and may therefore present as a sudden unexpected death in an elderly person. The amyloid is deposited in cortical blood vessels, and on hematoxylin-eosin sections takes the form of pink hyaline thickening of arteries and arterioles, often with narrowing of the lumina. For diagnosis apple-green birefringence after Congo red staining is the most widely practiced and reliable tool. CAA-related hemorrhage may also occur in any lobe of the cerebrum close to the external surface and may occur at multiple sites and at the same or different times. CAA-related hemorrhage may occur in the setting of trauma necessitating distinction between the two and raising the question of whether it precipitated trauma or vice versa. Usually CAA-related hemorrhage is infrequent in sites where traumatic hemorrhages occur, and traumatic hemorrhages are often associated with other hemorrhages in sites typical for trauma. Five cases demonstrating many of the clinical and pathological features of CAA-related hemorrhage are presented. In two of the five cases, the hemorrhage followed trauma, suggesting that trauma as a precipitating factor for CAA-related hemorrhage may be more common than is generally recognized. CAA-associated hemorrhage should be considered in the differential diagnosis of cerebral hemorrhage in the elderly whether or not dementia is present.     

A study of cerebral perfusion using single photon emission computed tomography in neonates with brain lesions

In this study we used a single photon emission computed tomography technique (SPECT) with radiolabelled 99mTcHMPAO to assess cerebral perfusion in newborn infants with documented cerebral lesions and to determine to what extent brain SPECT might be useful in the neonatal period. A total of 15 newborn infants with the following cerebral pathologies were enrolled: severe parietal bilateral periventricular leucomalacia (PVL, n = 6); moderate parietal bilateral PVL (n = 2); intraventricular haemorrhage grade II with unilateral parietal parenchymal extension (IHV + PE, n = 3); cerebral infarction (CI, n = 2) in the zone of middle cerebral artery; and post-haemorrhagic hydrocephalus (n = 2). Follow-up was available in all infants. Alterations in cerebral perfusion were seen in only 12 of 15 infants and at the location of severe PVL, PE and CI. We have noted that the regions of diminished perfusion extended beyond the apparent extent of cerebral pathology delineated by ultrasound or magnetic resonance imaging. Markedly diminished perfusion was seen in 1 infant with hydrocephalus, which recovered following placement of ventriculo-peritoneal shunt. Regarding outcome, SPECT data failed to provide additional information than that of neuroradiological investigations. We conclude that the use of SPECT, under these conditions, to assess alteration of cerebral perfusion in the neonatal period will not provide any additional information than that of neuroradiological investigations.     

Variations in fatty acids, tocopherol and other quality parameters of virgin olive oil subjected to refining process

Rare patterns of heroin-associated lesions within the central nervous system are described. In one case, magnetic resonance imaging revealed the combination of a border zone infarct within the thoracal spinal cord and a bilateral lesion within the globus pallidus. In a second case, cerebral border zone infarctions were observed which were attributed to a vasospasm of the basal cerebral arteries. Drug-abuse should be considered as a potential cause of these unusual manifestations of ischemic lesions in young patients.     

Histopathological studies of senile plaques and cerebral amyloidosis in cynomolgus monkeys

Senile plaques (SPs) and cerebral amyloid angiopathy (CAA), pathological hallmarks of Alzheimer's disease, have not been thoroughly investigated histopathologically in nonhuman primates. To determine the onset age and histopathological characteristics of SPs and CAA, we examined the brains of 64 cynomolgus monkeys (Macaca fascicularis) from 2 to 35 years old. Mature (classical and primitive) plaques appeared in 16 out of 25 monkeys that were >20 years old. Moreover, mature plaques were observed more frequently than diffuse plaques and were located in the temporal cortex of the superior or inferior gyri and amygdala. Diffuse plaques in contrast to mature plaques did not show definite tendencies in onset age and distribution. CAA appeared in more than 22-year-old monkeys in 10 out of 16 animals and was frequently observed in capillaries and often found adjoining mature plaques. During immunohistochemical examination, an antiserum for amyloid beta protein (A beta) 1-40 could detect all SPs, whereas a monoclonal antibody for A beta 8-17 could not detect any diffuse plaques and only one third of the primitive plaques. As for CAA, the polyclonal antiserum was more sensitive than the monoclonal antibody. The present study describes the histopathological features of SPs and CAA in old cynomolgus monkeys.     

The incidental nonhyperfunctioning adrenal mass: an imaging algorithm for characterization

Nonhyperfunctioning adrenal lesions such as cysts, myelolipomas, adrenal haemorrhage, adenoma and metastases are described. Definitive imaging features that help characterize adrenal cysts, myelolipomas and adrenal haemorrhage are illustrated and the differentiation of benign from malignant adrenal lesions using an algorithmic approach based on lipid sensitive imaging is provided.